U.S. patent number 8,784,385 [Application Number 12/586,076] was granted by the patent office on 2014-07-22 for frozen piercing implements and methods for piercing a substrate.
This patent grant is currently assigned to The Invention Science Fund I, LLC. The grantee listed for this patent is Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney, Lowell L. Wood, Jr.. Invention is credited to Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney, Lowell L. Wood, Jr..
United States Patent |
8,784,385 |
Boyden , et al. |
July 22, 2014 |
Frozen piercing implements and methods for piercing a substrate
Abstract
Certain embodiments disclosed herein relate to compositions,
methods, devices, systems, and products regarding frozen particles.
In certain embodiments, the frozen particles include materials at
low temperatures. In certain embodiments, the frozen particles
provide vehicles for delivery of particular agents. In certain
embodiments, the frozen particles are administered to at least one
biological tissue.
Inventors: |
Boyden; Edward S. (Cambridge,
MA), Cook; Daniel B. (Seattle, WA), Hyde; Roderick A.
(Redmond, WA), Leuthardt; Eric C. (St. Louis, MO),
Myhrvold; Nathan P. (Bellevue, WA), Sweeney; Elizabeth
A. (Seattle, WA), Wood, Jr.; Lowell L. (Bellevue,
WA) |
Applicant: |
Name |
City |
State |
Country |
Type |
Boyden; Edward S.
Cook; Daniel B.
Hyde; Roderick A.
Leuthardt; Eric C.
Myhrvold; Nathan P.
Sweeney; Elizabeth A.
Wood, Jr.; Lowell L. |
Cambridge
Seattle
Redmond
St. Louis
Bellevue
Seattle
Bellevue |
MA
WA
WA
MO
WA
WA
WA |
US
US
US
US
US
US
US |
|
|
Assignee: |
The Invention Science Fund I,
LLC (Bellevue, WA)
|
Family
ID: |
46332330 |
Appl.
No.: |
12/586,076 |
Filed: |
September 15, 2009 |
Prior Publication Data
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Document
Identifier |
Publication Date |
|
US 20100111855 A1 |
May 6, 2010 |
|
Related U.S. Patent Documents
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Application
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Patent Number |
Issue Date |
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Current U.S.
Class: |
604/173 |
Current CPC
Class: |
A61K
9/0019 (20130101); A61P 35/00 (20180101); C07K
16/283 (20130101); A61K 31/74 (20130101); C07K
16/2878 (20130101); A61K 41/0004 (20130101); A61M
37/0015 (20130101); A61K 39/145 (20130101); A61K
38/4833 (20130101); A61P 31/16 (20180101); A61K
9/19 (20130101); A61K 31/70 (20130101); A61K
31/7088 (20130101); A61K 9/1664 (20130101); A61K
9/08 (20130101); A61K 31/00 (20130101); G16H
30/40 (20180101); A61K 39/12 (20130101); A61K
9/007 (20130101); C07K 16/2842 (20130101); A61K
9/12 (20130101); A61K 9/143 (20130101); A61K
9/2866 (20130101); G16H 50/20 (20180101); A61K
9/1688 (20130101); A61K 9/1641 (20130101); A61P
17/02 (20180101); A61K 9/0021 (20130101); A61K
45/06 (20130101); A61K 9/209 (20130101); A61K
9/2095 (20130101); A61K 9/1611 (20130101); A61K
33/00 (20130101); C07K 16/22 (20130101); C07K
16/30 (20130101); G16H 50/50 (20180101); A61K
31/337 (20130101); A61K 38/38 (20130101); A61K
31/337 (20130101); A61K 2300/00 (20130101); A61M
37/0015 (20130101); A61M 2205/02 (20130101); A61K
31/70 (20130101); A61K 2300/00 (20130101); A61K
31/7088 (20130101); A61K 2300/00 (20130101); A61M
2037/003 (20130101); C12N 2760/16034 (20130101); A61M
2205/02 (20130101); A61K 2039/505 (20130101); A61K
31/505 (20130101); Y02A 90/10 (20180101); Y02A
50/30 (20180101); B33Y 80/00 (20141201); A61K
39/00 (20130101); G16H 20/10 (20180101); Y10T
83/222 (20150401); A61K 38/4886 (20130101); A61K
31/519 (20130101); A61M 2037/0023 (20130101); A61K
31/59 (20130101); A61K 2039/54 (20130101) |
Current International
Class: |
A61M
37/00 (20060101) |
Field of
Search: |
;604/173 |
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|
Primary Examiner: Harward; Soren
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is related to and claims the benefit of the
earliest available effective filing date(s) from the following
listed application(s) (the "Related Applications") (e.g., claims
earliest available priority dates for other than provisional patent
applications or claims benefits under 35 USC .sctn.119(e) for
provisional patent applications, for any and all parent,
grandparent, great-grandparent, etc. applications of the Related
Application(s)). All subject matter of the Related Applications and
of any and all parent, grandparent, great-grandparent, etc.
applications of the Related Applications is incorporated herein by
reference to the extent such subject matter is not inconsistent
herewith.
RELATED APPLICATIONS
For purposes of the USPTO extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/290,671, entitled COMPOSITIONS AND METHODS
FOR THERAPEUTIC DELIVERY WITH FROZEN PARTICLES, naming Edward S.
Boyden, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold,
Elizabeth A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31
Oct. 2008, which is currently co-pending, or is an application of
which a currently co-pending application is entitled to the benefit
of the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,683, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,685, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,686, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,690, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,691, entitled COMPOSITIONS AND METHODS FOR THERAPEUTIC
DELIVERY WITH FROZEN PARTICLES, naming Edward S. Boyden, Roderick
A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A.
Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct. 2008,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,684, now U.S. Pat. No. 8,731,840 entitled COMPOSITIONS AND
METHODS FOR THERAPEUTIC DELIVERY WITH FROZEN PARTICLES, naming
Edward S. Boyden, Roderick A. Hyde, Eric C. Leuthardt, Nathan P.
Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Oct. 2008, which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,670, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,664, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,659, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, now U.S.Pat. No. 8,403,376 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,658, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,665, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,677, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, now U.S. Pat. No. 8,721,583 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,687, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, now U.S. Pat. No. 8,725,420 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/290,676, entitled COMPOSITIONS AND METHODS FOR SURFACE ABRASION
WITH FROZEN PARTICLES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 31 Oct.
2008, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,264, entitled COMPOSITIONS AND METHODS FOR DELIVERY OF
FROZEN PARTICLE ADHESIVES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 20 Mar.
2009, now U.S. Pat. No. 8,545,856 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,263, entitled COMPOSITIONS AND METHODS FOR DELIVERY OF
FROZEN PARTICLE ADHESIVES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 20 Mar.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,260, entitled COMPOSITIONS AND METHODS FOR DELIVERY OF
FROZEN PARTICLE ADHESIVES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 20 Mar.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,265, entitled COMPOSITIONS AND METHODS FOR DELIVERY OF
FROZEN PARTICLE ADHESIVES, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 20 Mar.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,851, entitled COMPOSITIONS AND METHODS FOR ADMINISTERING
COMPARTMENTALIZED FROZEN PARTICLES, naming Edward S. Boyden, Daniel
B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold,
Elizabeth A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 27
Mar. 2009, now U.S. Pat. No. 8,551,506 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,863, entitled COMPOSITIONS AND METHODS FOR ADMINISTERING
COMPARTMENTALIZED FROZEN PARTICLES, naming Edward S. Boyden, Daniel
B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold,
Elizabeth A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 27
Mar. 2009, now U.S. Pat. No. 8,603,494 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,821, entitled COMPOSITIONS AND METHODS FOR ADMINISTERING
COMPARTMENTALIZED FROZEN PARTICLES, naming Edward S. Boyden, Daniel
B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold,
Elizabeth A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 27
Mar. 2009, now U.S. Pat. No. 8,545,857 which is currently, or is an
application of which a currently application is entitled to the
benefit of the filing date. For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/383,829, entitled COMPOSITIONS AND METHODS FOR ADMINISTERING
COMPARTMENTALIZED FROZEN PARTICLES, naming Edward S. Boyden, Daniel
B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold,
Elizabeth A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 27
Mar. 2009, now U.S. Pat. No. 8,563,012 which is currently
co-pending, or is an application of which a currently co-pending
application is entitled to the benefit of the filing date. For
purposes of the USPTO extra-statutory requirements, the present
application constitutes a continuation-in-part of U.S. patent
application Ser. No. 12/384,202, entitled COMPOSITIONS AND METHODS
FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLE, COMPOSITIONS,
naming Edward S. Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C.
Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney and Lowell L.
Wood, Jr. as inventors, filed 31 Mar. 2009, now U.S. Pat. No.
8,603,496 which is currently, or is an application of which a
currently application is entitled to the benefit of the filing
date. For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S
patent application Ser. No. 12/384,201, entitled COMPOSITIONS AND
METHODS FOR BIOLOGICAL REMODELING WITH FROZEN PARTICLE
COMPOSITIONS, naming Edward S. Boyden, Daniel B. Cook, Roderick A.
Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney
and Lowell L. Wood, Jr. as inventors, filed 31 Mar. 2009, now U.S.
Pat. No. 8,603,495 which is currently, or is an application of
which a currently application is entitled to the benefit of the
filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/384,212, entitled COMPOSITIONS AND METHODS FOR BIOLOGICAL
REMODELING WITH FROZEN PARTICLE COMPOSITIONS, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Mar. 2009, now U.S. Pat. No. 8,545,806 which is
currently, or is an application of which a currently application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/384,215, entitled COMPOSITIONS AND METHODS FOR BIOLOGICAL
REMODELING WITH FROZEN PARTICLE COMPOSITIONS, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Mar. 2009, now U.S. Pat. No. 8,613,937 which is
currently, or is an application of which a currently application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/384,218, entitled COMPOSITIONS AND METHODS FOR BIOLOGICAL
REMODELING WITH FROZEN PARTICLE COMPOSITIONS, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Mar. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/384,214, entitled COMPOSITIONS AND METHODS FOR BIOLOGICAL
REMODELING WITH FROZEN PARTICLE COMPOSITIONS, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Mar. 2009, now U.S. Pat. No. 8,731,842 which is
currently, or is an application of which a currently application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser
No. 12/384,216, entitled COMPOSITIONS AND METHODS FOR BIOLOGICAL
REMODELING WITH FROZEN PARTICLE COMPOSITIONS, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 31 Mar. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/586,074, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/586,070, entitled FROZEN COMPOSITIONS AND METHODS FOR PIERCING
A
SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook, Roderick A.
Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney
and Lowell L. Wood, Jr. as inventors, filed 15 Sep. 2009, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date. For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/586,072, entitled FROZEN
COMPOSITIONS AND METHODS FOR PIERCING A SUBSTRATE, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 15 Sep. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/586,073, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date. For purposes of the USPTO extra-statutory
requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No.
12/586,077, entitled FROZEN COMPOSITIONS AND METHODS FOR PIERCING A
SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook, Roderick A.
Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth A. Sweeney
and Lowell L. Wood, Jr. as inventors, filed 15 Sep. 2009, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date. For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/586,075, entitled FROZEN
COMPOSITIONS AND METHODS FOR PIERCING A SUBSTRATE, naming Edward S.
Boyden, Daniel B. Cook, Roderick A. Hyde, Eric C. Leuthardt, Nathan
P. Myhrvold, Elizabeth A. Sweeney and Lowell L. Wood, Jr. as
inventors, filed 15 Sep. 2009, which is currently co-pending, or is
an application of which a currently co-pending application is
entitled to the benefit of the filing date. For purposes of the
USPTO extra-statutory requirements, the present application
constitutes a continuation-in-part of U.S. patent application Ser.
No. 12/586,071, entitled FROZEN COMPOSITIONS AND METHODS FOR
PIERCING A SUBSTRATE, naming Edward S. Boyden, Daniel B. Cook,
Roderick A. Hyde, Eric C. Leuthardt, Nathan P. Myhrvold, Elizabeth
A. Sweeney and Lowell L. Wood, Jr. as inventors, filed 15 Sep.
2009, which is currently co-pending, or is an application of which
a currently co-pending application is entitled to the benefit of
the filing date.
Claims
What is claimed is:
1. A sterile frozen hydrogen oxide piercing implement, comprising:
sterile frozen hydrogen oxide having a height to width ratio of
greater than or equal to 1.5:1 wherein the frozen hydrogen oxide
piercing implement consists essentially of frozen ice and at least
one agent, and includes at least one substantially hydrophilic
channel; and wherein the implement is attached to a support
structure.
2. The sterile frozen hydrogen oxide piercing implement of claim 1,
wherein the implement has at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer, or any value therebetween.
3. The sterile frozen hydrogen oxide piercing implement of claim 1,
wherein the at least one agent includes at least one of a
therapeutic agent, explosive material, adhesive agent, biological
remodeling agent, or abrasive.
4. The sterile frozen hydrogen oxide piercing implement of claim 1,
wherein the at least one agent is included as an outer coating of
the frozen hydrogen oxide piercing implement.
5. The frozen piercing implement of claim 1, wherein the at least
one agent is encapsulated within the frozen piercing implement.
6. The sterile frozen hydrogen oxide piercing implement of claim 1,
wherein the at least one agent includes one or more of a prodrug or
precursor compound.
7. The sterile frozen hydrogen oxide piercing implement of claim 1,
wherein the sterile frozen hydrogen oxide is substantially in one
or more phases including at least one of amorphous solid water, low
density amorphous ice, high density amorphous ice, very high
density amorphous ice, clathrate ice, hyperquenched glassy water,
ice Ic, ice Ih, ice II, ice III, ice IV, ice V, ice VI, ice VII,
ice VIII, ice IX, ice X, ice XI, ice XII, ice XIII, ice XIV, or ice
XV.
8. The frozen piercing implement of claim 1, wherein the frozen
piercing implement includes at least one cavity.
9. The sterile frozen hydrogen oxide piercing implement of claim 1,
further including at least one detection material.
10. The sterile frozen hydrogen oxide piercing implement of claim
9, wherein the at least one detection material includes at least
one of a contrast agent, sensor, or electronic identification
device.
11. The sterile frozen hydrogen oxide piercing implement of claim
10, wherein the at least one electronic identification device
includes at least one radio frequency identification device.
12. The frozen piercing implement of claim 9, wherein the at least
one detection material includes at least one temperature-sensitive
substance.
13. The frozen piercing implement of claim 9, wherein the at least
one detection material includes at least one of a radioactive,
luminescent, colorimetric or odorous substance.
14. The frozen piercing implement of claim 1, wherein the at least
one frozen piercing implement includes one or more layers.
15. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the at least one implement is configured to melt or
evaporate prior to, during, or subsequent to contacting the at
least one substrate.
16. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the at least one implement is configured to melt within
the at least one substrate.
17. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the at least one implement is configured to be
substantially removed from the at least one substrate.
18. The sterile frozen hydrogen oxide piercing implement of claim
1, further including at least one non-frozen implement holding
device.
19. The sterile frozen hydrogen oxide piercing implement of claim
18, wherein the at least one non-frozen implement holding device
includes at least one handle, robotic arm, or surgical device.
20. The frozen piercing implement of claim 1, wherein the frozen
piercing implement includes at least one port.
21. The frozen piercing implement of claim 20, wherein the at least
one port includes at least one side port.
22. The frozen piercing implement of claim 20, wherein the at least
one port includes at least one end port.
23. The frozen piercing implement of claim 20, wherein the at least
one port includes at least one inlet port or outlet port.
24. The frozen piercing implement of claim 20, wherein the at least
one inlet port or outlet port is in fluid communication with at
least one channel.
25. The sterile frozen hydrogen oxide piercing implement of claim
1, formulated to be administered to the at least one substrate.
26. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the at least one substrate includes one or more of a
cell, tissue, organ, structure, device, or food product.
27. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the at least one frozen piercing implement includes at
least one sensor.
28. The sterile frozen hydrogen oxide piercing implement of claim
27, wherein the at least one sensor includes at least one sensor
configured for detecting at least one of a biochemical, electrical,
optical, functional, physical, chemical, biological, or structural
characteristic of the at least one material.
29. The sterile frozen hydrogen oxide piercing implement of claim
1, further including a plurality of frozen piercing implements.
30. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the frozen piercing implement is included in at least
one frozen piercing implement device.
31. The sterile frozen hydrogen oxide piercing implement of claim
1, wherein the agent includes one or more of an anti-coagulant, a
vaccine, an adjuvant, an anti-agiogenic factor, an
anti-inflammatory, an analgesic, or an anti-tumor agent.
Description
The United States Patent Office (USPTO) has published a notice to
the effect that the USPTO's computer programs require that patent
applicants reference both a serial number and indicate whether an
application is a continuation or continuation-in-part. Stephen G.
Kunin, Benefit of Prior-Filed Application, USPTO Official Gazette
Mar. 18, 2003. The present Applicant Entity (hereinafter
"Applicant") has provided above a specific reference to the
application(s) from which priority is being claimed as recited by
statute. Applicant understands that the statute is unambiguous in
its specific reference language and does not require either a
serial number or any characterization, such as "continuation" or
"continuation-in-part," for claiming priority to U.S. patent
applications. Notwithstanding the foregoing, Applicant understands
that the USPTO's computer programs have certain data entry
requirements, and hence Applicant is designating the present
application as a continuation-in-part of its parent applications as
set forth above, but expressly points out that such designations
are not to be construed in any way as any type of commentary and/or
admission as to whether or not the present application contains any
new matter in addition to the matter of its parent
application(s).
SUMMARY
Compositions, methods, systems, and other embodiments related to
one or more frozen particle compositions are described herein. In
one embodiment, frozen particle compositions, frozen piercing
implements, or frozen piercing implement devices are described.
In one embodiment, a frozen piercing implement comprising a sterile
frozen implement configured for piercing at least one substrate is
described. In one embodiment, a frozen piercing implement,
comprises: a sterile frozen hydrogen oxide implement configured for
piercing at least part of at least one substrate. In one
embodiment, the sterile frozen hydrogen oxide implement includes at
least one agent.
In one embodiment, a method of administering at least one frozen
piercing implement to at least one substrate comprises: contacting
at least one substrate with at least one frozen piercing implement.
In one embodiment, the at least one frozen piercing implement
includes sterile frozen hydrogen oxide. In one embodiment, a method
of vaccinating a subject comprises: administering to a subject at
least one frozen piercing implement. In one embodiment, the at
least one frozen piercing implement includes sterile frozen
hydrogen oxide and at least one vaccine. In one embodiment, a
method comprises: delivering at least one agent to at least one
substrate; wherein the at least one agent is included in at least
one sterile frozen hydrogen oxide piercing implement. In one
embodiment, a method for piercing at least one substrate comprises:
piercing at least one substrate with a frozen piercing implement
including sterile frozen hydrogen oxide and at least one agent.
In one embodiment, a frozen piercing implement, comprises: at least
one sterile frozen solution, the solution including at least one
agent; wherein the frozen piercing implement is configured for
piercing at least part of at least one substrate. In one
embodiment, a method of administering at least one frozen piercing
implement to at least one substrate, comprises: contacting at least
one substrate with at least one frozen piercing implement, wherein
the at least one frozen piercing implement includes at least one
sterile frozen solution, the solution including at least one agent.
In one embodiment, a method of vaccinating a subject, comprises:
administering to a subject at least one frozen piercing implement;
wherein the at least one frozen piercing implement includes at
least one sterile frozen solution, the solution including at least
one vaccine.
In one embodiment, a frozen piercing implement comprises: at least
one non-hydrogen oxide frozen solvent; wherein the frozen piercing
implement is configured for piercing at least one substrate; and
wherein the frozen piercing implement is substantially solid at
approximately 65.degree. C., approximately 60.degree. C.,
approximately 55.degree. C., approximately 50.degree. C.,
approximately 45.degree. C., approximately 40.degree. C.,
approximately 37.degree. C., approximately 35.degree. C.,
approximately 30.degree. C., approximately 25.degree. C.,
approximately 20.degree. C., approximately 15.degree. C.,
approximately 10.degree. C., approximately 5.degree. C.,
approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one non-hydrogen oxide frozen solvent
is sterile. In one embodiment, the at least one non-hydrogen oxide
frozen solvent includes at least one agent
In one embodiment, a frozen piercing implement, comprises: at least
one frozen agent; and wherein the frozen piercing implement is
configured for piercing at least one substrate wherein the frozen
piercing implement is substantially solid at approximately
65.degree. C., approximately 60.degree. C., approximately
55.degree. C., approximately 50.degree. C., approximately
45.degree. C., approximately 40.degree. C., approximately
37.degree. C., approximately 35.degree. C., approximately
30.degree. C., approximately 25.degree. C., approximately
20.degree. C., approximately 15.degree. C., approximately
10.degree. C., approximately 5.degree. C., approximately 0.degree.
C., approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween.
In one embodiment, a method of administering at least one frozen
piercing implement to at least one substrate, comprises: contacting
at least one substrate with at least one frozen piercing implement,
wherein the at least one frozen piercing implement includes at
least one non-hydrogen oxide frozen solvent; and wherein the at
least one frozen piercing implement is substantially solid at
approximately 65.degree. C., approximately 60.degree. C.,
approximately 55.degree. C., approximately 50.degree. C.,
approximately 45.degree. C., approximately 40.degree. C.,
approximately 37.degree. C., approximately 35.degree. C.,
approximately 30.degree. C., approximately 25.degree. C.,
approximately 20.degree. C., approximately 15.degree. C.,
approximately 10.degree. C., approximately 5.degree. C.,
approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one non-hydrogen oxide frozen solvent
is sterile. In one embodiment, the at least one non-hydrogen oxide
frozen solvent includes at least one agent.
In one embodiment, a method of administering at least one frozen
piercing implement to at least one substrate, comprises:contacting
at least one substrate with at least one frozen piercing implement,
wherein the at least one frozen piercing implement includes at
least one agent; and wherein the at least one frozen piercing
implement is substantially solid at approximately 65.degree. C.,
approximately 60.degree. C., approximately 55.degree. C.,
approximately 50.degree. C., approximately 45.degree. C.,
approximately 40.degree. C., approximately 37.degree. C.,
approximately 35.degree. C., approximately 30.degree. C.,
approximately 25.degree. C., approximately 20.degree. C.,
approximately 15.degree. C., approximately 10.degree. C.,
approximately 5.degree. C., approximately 0.degree. C.,
approximately -5.degree. C., approximately -10.degree. C.,
approximately -15.degree. C., approximately -20.degree. C.,
approximately -25.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -80.degree. C., approximately -90.degree. C.,
approximately -100.degree. C., approximately -120.degree. C.,
approximately -150.degree. C., approximately -170.degree. C.,
approximately -200.degree. C., approximately -250.degree. C., or
any temperature therebetween.
In one embodiment, a method of vaccinating a subject, comprises:
administering to a subject at least one frozen piercing implement;
wherein the at least one frozen piercing implement includes at
least one non-hydrogen oxide frozen solvent and at least one
vaccine; and wherein the at least one frozen piercing implement is
substantially solid at approximately 65.degree. C., approximately
60.degree. C., approximately 55.degree. C., approximately
50.degree. C., approximately 45.degree. C., approximately
40.degree. C., approximately 37.degree. C., approximately
35.degree. C., approximately 30.degree. C., approximately
25.degree. C., approximately 20.degree. C., approximately
15.degree. C., approximately 10.degree. C., approximately 5.degree.
C., approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, a method of vaccinating a subject, comprises:
administering to a subject at least one frozen vaccine piercing
implement; wherein the at least one frozen piercing implement is
substantially solid at approximately 65.degree. C., approximately
60.degree. C., approximately 55.degree. C., approximately
50.degree. C., approximately 45.degree. C., approximately
40.degree. C., approximately 37.degree. C., approximately
35.degree. C., approximately 30.degree. C., approximately
25.degree. C., approximately 20.degree. C., approximately
15.degree. C., approximately 10.degree. C., approximately 5.degree.
C., approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one frozen piercing implement is
sterile. In one embodiment, the at least one frozen piercing
implement includes at least one agent.
In one embodiment, a frozen piercing implement, comprises: at least
one sterile frozen component and at least one agent; wherein the at
least one component is substantially in a gaseous state at or above
approximately 0.25 bar, approximately 0.5 bar, approximately 1.0
bar, approximately 5.0 bar, approximately 10.0 bar, approximately
25 bar, approximately 50 bar, approximately 100 bar, approximately
200 bar, or approximately 500 bar pressure; and at or above
approximately 10.degree. C., approximately 15.degree. C.,
approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing at least one
substrate.
In one embodiment, a method of administering at least one frozen
piercing implement to at least one substrate, comprises: contacting
at least one substrate with at least one frozen piercing implement,
wherein the at least one frozen piercing implement includes at
least one sterile frozen component and at least one agent; wherein
the at least one sterile frozen component is in a gaseous state at
approximately 0.25 bar, approximately 0.5 bar, approximately 1.0
bar, approximately 5.0 bar, approximately 10.0 bar, approximately
25 bar, approximately 50 bar, approximately 100 bar, approximately
200 bar, or approximately 500 bar pressure; and at or above
approximately 10.degree. C., approximately 15.degree. C.,
approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing the at least one
substrate.
In one embodiment, a method of vaccinating a subject, comprises:
administering to a subject at least one frozen piercing implement;
wherein the at least one frozen piercing implement includes at
least one sterile frozen component and at least one agent; and
wherein the at least one sterile frozen component is in a gaseous
state at approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing at least one
substrate.
In one embodiment, an array device comprises: a support structure
having a surface; and a plurality of sterile frozen piercing
implements extending substantially outward from the support
structure. In one embodiment, an array device, comprises: a support
structure having a surface; a plurality of piercing implements
extending substantially outward from the surface of the support
structure; wherein at least one piercing implement of the plurality
of piercing implements includes a frozen piercing implement. In one
embodiment, a composition, comprises: a plurality of piercing
implement array devices joined together, the piercing implement
array devices including at least one frozen piercing implement. In
one embodiment, a composition, comprises: a support means for an
array device; wherein the array device includes one or more frozen
piercing implements. In one embodiment, a method of administering
at least one array device to at least one substrate, comprises:
contacting at least one array device to at least one substrate,
wherein the array device includes at least one frozen piercing
implement.
In one embodiment, a method of vaccinating a subject, comprises:
administering to a subject at least one frozen piercing implement
array device; wherein the at least one frozen piercing implement
array device includes at least one frozen piercing implement
including at least one vaccine.
In one embodiment, a fluidic device, comprises: a support structure
at least partially defining at least one compartment; and at least
one frozen piercing implement in fluid communication with the at
least one compartment. As described herein, in one embodiment, the
at least one frozen piercing implement has at least one major
dimension of approximately one centimeter or less, approximately
one millimeter or less, approximately one micrometer or less,
approximately one nanometer, or any value therebetween.
In one embodiment, a fluidic device, comprises: at least one frozen
piercing implement, and at least one actuator configured to actuate
the at least one frozen piercing implement. As described herein, in
one embodiment, at least one frozen piercing implement has at least
one major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer, or any value
therebetween.
In one embodiment, the fluidic device further comprises a plurality
of frozen piercing implements, and at least one actuator configured
to actuate the plurality of frozen piercing implements; wherein
each piercing implement has at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer, or any value therebetween.
Various computer-implemented methods, automated devices, systems,
computer program products, and circuitry for any thereof are
provided herein. In one embodiment, instructions for making at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device are provided for various
non-limiting examples. In one embodiment, instructions for
administering at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device are
provided for various non-limiting examples.
The various embodiments disclosed are described in greater detail
herein.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 illustrates particular phases of hydrogen oxide.
FIG. 2 illustrates the density of hydrogen oxide at various
pressure points.
FIG. 3 illustrates particular phases of hydrogen oxide at various
pressure and temperature points.
FIG. 4 illustrates particular phases of hydrogen oxide at various
pressure and temperature points.
FIG. 5 illustrates the strength of hydrogen oxide samples
reinforced with fiberglass or kaolin.
FIG. 6 illustrates the strength of hydrogen oxide samples
reinforced with a reinforcement agent.
FIG. 7 illustrates a partial view of a method 700 that includes
generating at least one response.
FIG. 8 illustrates a partial view of FIG. 7 in which embodiments
may be implemented.
FIG. 9 illustrates a partial view of FIG. 7 in which embodiments
may be implemented.
FIG. 10 illustrates a partial view of a method 1000 that includes
generating at least one response.
FIG. 11 illustrates a partial view of FIG. 10 in which embodiments
may be implemented.
FIG. 12 illustrates a partial view of FIG. 10 in which embodiments
may be implemented.
FIG. 13 illustrates a partial view of a system 1300 that includes a
computer program for executing a computing process on a computing
device.
FIG. 14 illustrates a partial view of FIG. 13 in which embodiments
may be implemented.
FIG. 15 illustrates a partial view of FIG. 13 in which embodiments
may be implemented.
FIG. 16 illustrates a partial view of a system 1600 that includes a
computer program for executing a computing process on a computing
device.
FIG. 17 illustrates a partial view of a computer program product
1700 for executing a computing process on a computing device.
FIG. 18 illustrates a partial view of a computer program product
1800 for executing a computing process on a computing device.
FIG. 19 illustrates a partial view of a computer program product
1900 for executing a computing process on a computing device.
FIG. 20 illustrates a partial view of a computer program product
2000 for executing a computing process on a computing device.
FIG. 21 illustrates a partial view of a computer program product
2100 for executing a computing process on a computing device.
FIG. 22 illustrates a partial view of a computer program product
2200 for executing a computing process on a computing device.
FIG. 23 illustrates a partial view of a method 2300 that includes
generating at least one response.
FIG. 24 illustrates a partial view FIG. 23 in which embodiments may
be implemented.
FIG. 25 illustrates a partial view FIG. 23 in which embodiments may
be implemented.
FIG. 26 illustrates a partial view of a method 2600 that includes
generating at least one response.
FIG. 27 illustrates a partial view of FIG. 26 in which embodiments
may be implemented.
FIG. 28 illustrates a partial view of FIG. 26 in which embodiments
may be implemented.
FIG. 29 illustrates a partial view of a system 2900 that includes a
computer program for executing a computing process on a computing
device.
FIG. 30 illustrates a partial view of FIG. 29 in which embodiments
may be implemented.
FIG. 31 illustrates a partial view of a system 3100 that includes a
computer program for executing a computing process on a computing
device.
FIG. 32 illustrates a partial view of FIG. 31 in which embodiments
may be implemented.
FIG. 33 illustrates a partial view of a system 3300 that includes a
computer program for executing a computing process on a computing
device.
FIG. 34 illustrates a partial view of FIG. 33 in which embodiments
may be implemented.
FIG. 35 illustrates a partial view of FIG. 33 in which embodiments
may be implemented.
FIG. 36 illustrates a partial view of a system 3600 that includes a
computer program for executing a computing process on a computing
device.
FIG. 37 illustrates a partial view of a method 3700 in which
embodiments may be implemented.
FIG. 38 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 39 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 40 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 41 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 42 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 43 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 44 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 45 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 46 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 47 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 48 illustrates a partial view of FIG. 37 in which embodiments
may be implemented.
FIG. 49 illustrates a partial view of a method 4900 in which
embodiments may be implemented.
FIG. 50 illustrates a partial view of FIG. 49 in which embodiments
may be implemented.
FIG. 51 illustrates a partial view of FIG. 49 in which embodiments
may be implemented.
FIG. 52 illustrates a partial view of FIG. 49 in which embodiments
may be implemented.
FIG. 53 illustrates a partial view of FIG. 49 in which embodiments
may be implemented.
FIG. 54 illustrates a partial view of a method 5400 in which
embodiments may be implemented.
FIG. 55 illustrates a partial view of FIG. 54 in which embodiments
may be implemented.
FIG. 56 illustrates a partial view of FIG. 54 in which embodiments
may be implemented.
FIG. 57 illustrates a partial view of FIG. 54 in which embodiments
may be implemented.
FIG. 58 illustrates a partial view of FIG. 54 in which embodiments
may be implemented.
FIG. 59 illustrates a partial view of a method 5900 in which
embodiments may be implemented.
FIG. 60 illustrates a partial view of a method 6000 in which
embodiments may be implemented.
FIG. 61 illustrates a partial view of FIG. 60 in which embodiments
may be implemented.
FIG. 62 illustrates a partial view of FIG. 60 in which embodiments
may be implemented.
FIG. 63 illustrates a partial view of FIG. 60 in which embodiments
may be implemented.
FIG. 64 illustrates a partial view of FIG. 60 in which embodiments
may be implemented.
FIG. 65 illustrates a partial view of FIG. 60 in which embodiments
may be implemented.
FIG. 66 illustrates a partial view of a method 6600 in which
embodiments may be implemented.
FIG. 67 illustrates a partial view of FIG. 66 in which embodiments
may be implemented.
FIG. 68 illustrates a partial view of FIG. 66 in which embodiments
may be implemented.
FIG. 69 illustrates a partial view of FIG. 66 in which embodiments
may be implemented.
FIG. 70 illustrates a partial view of FIG. 66 in which embodiments
may be implemented.
FIG. 71 illustrates a partial view of FIG. 66 in which embodiments
may be implemented.
FIG. 72 illustrates a partial view of FIG. 66 in which embodiments
may be implemented.
FIG. 73 illustrates a partial view of a system 7300 in which
embodiments may be implemented.
FIG. 74 illustrates a partial view of FIG. 73 in which embodiments
may be implemented.
FIG. 75 illustrates a partial view of a system 7510 in which
embodiments may be implemented.
FIG. 76 illustrates a partial view of FIG. 75 in which embodiments
may be implemented.
FIG. 77 illustrates a partial view of a system 7700 in which
embodiments may be implemented.
FIG. 78 illustrates a partial view of a computer program product
7800 in which embodiments may be implemented.
FIG. 79 illustrates a partial view of a system 7900 in which
embodiments may be implemented.
FIG. 80 illustrates a partial view of a system 8000 in which
embodiments may be implemented.
FIG. 81 illustrates a partial view of FIG. 80 in which embodiments
may be implemented.
FIG. 82 illustrates a partial view of a system 8200 in which
embodiments may be implemented.
FIG. 83 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 84 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 85 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 86 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 87 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 88 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 89 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 90 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 91 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 92 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 93 illustrates a partial view of FIG. 82 in which embodiments
may be implemented.
FIG. 94 illustrates a partial view of a system 9400 in which
embodiments may be implemented.
FIG. 95 illustrates a partial view of FIG. 94 in which embodiments
may be implemented.
FIG. 96 illustrates a partial view of FIG. 94 in which embodiments
may be implemented.
FIG. 97 illustrates a partial view of FIG. 94 in which embodiments
may be implemented.
FIG. 98 illustrates a partial view of FIG. 94 in which embodiments
may be implemented.
FIG. 99 illustrates a partial view of a system 9900 in which
embodiments may be implemented.
FIG. 100 illustrates a partial view of FIG. 99 in which embodiments
may be implemented.
FIG. 101 illustrates a partial view of FIG. 99 in which embodiments
may be implemented.
FIG. 102 illustrates a partial view of FIG. 99 in which embodiments
may be implemented.
FIG. 103 illustrates a partial view of FIG. 99 in which embodiments
may be implemented.
FIG. 104 illustrates a partial view of a system 10400 in which
embodiments may be implemented.
FIG. 105 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
FIG. 106 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
FIG. 107 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
FIG. 108 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
FIG. 109 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
FIG. 110 illustrates a partial view of FIG. 104 in which
embodiments may be implemented.
FIG. 111 illustrates a partial view of a system 11100 in which
embodiments may be implemented.
FIG. 112 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
FIG. 113 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
FIG. 114 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
FIG. 115 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
FIG. 116 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
FIG. 117 illustrates a partial view of FIG. 111 in which
embodiments may be implemented.
FIG. 118 illustrates a partial cross-sectional view of mammalian
skin.
FIG. 119 illustrates a general phase diagram, including the
critical point and sinodal curve.
FIG. 120 illustrates the boiling liquid expansion vapor explosion
diagram for carbon dioxide, calculated using the critical point and
sinodal curve.
FIG. 121 A illustrates particular examples of optional
configurations of embodiments including at least one frozen
particle composition or frozen piercing implement.
FIG. 121 B illustrates particular examples for configurations of
embodiments including at least one frozen particle composition or
frozen piercing implement with optional at least one cavity.
FIG. 121 C illustrates particular examples of optional
configurations of embodiments including at least one frozen
particle composition or frozen piercing implement.
FIG. 122 illustrates a diagram for a particular force per implement
for amount of displacement.
FIG. 123 illustrates perspective views of particular examples of
optional configurations of embodiments including at least one
frozen particle composition, frozen piercing implement, or frozen
piercing implement device.
FIG. 124 A illustrates an example of an embodiment including at
least one frozen piercing implement or frozen piercing implement
device.
FIG. 124 B illustrates an example of one embodiment for making at
least one frozen particle composition, frozen piercing implement or
frozen piercing implement device.
FIG. 124 C illustrates an example of one embodiment for making at
least one frozen particle composition, frozen piercing implement or
frozen piercing implement device.
FIG. 124 D illustrates an example of one embodiment for making at
least one frozen particle composition, frozen piercing implement or
frozen piercing implement device.
FIG. 124 E illustrates an example of one embodiment for making at
least one frozen particle composition, frozen piercing implement or
frozen piercing implement device.
FIG. 124 F illustrates an example of one embodiment for making at
least one frozen particle composition, frozen piercing implement or
frozen piercing implement device.
FIG. 124 G illustrates an example of one embodiment for making at
least one frozen particle composition, frozen piercing implement or
frozen piercing implement device.
FIG. 125 A illustrates cross-sectional view of a piercing implement
including one or more functionalized surfaces, and optional
channel, according to some illustrated embodiments.
FIG. 125 B illustrates cross-sectional view of a piercing implement
including one or more functionalized surfaces, and optional
channel, according to some illustrated embodiments.
FIG. 125 C illustrates cross-sectional view of a piercing implement
including one or more functionalized surfaces, and optional
channel, according to some illustrated embodiments.
FIG. 125 D illustrates an exploded view of the implement
illustrated in FIG. 125 C, including one or more functional groups
in the form of bonded amino groups, according to some illustrated
embodiments.
FIG. 125 E illustrates an exploded view of an implement, including
one or more functional groups in the form of polisilane groups,
according to some illustrated embodiments.
FIG. 126 A illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 126 B illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 126 C illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 126 D illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 126 E illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 126 F illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 126 G illustrates a cross-sectional view of a plurality of
implements, according to some illustrated embodiments.
FIG. 127 A illustrates a cross-sectional view of an embodiment
including at least one frozen piercing implement device.
FIG. 127 B illustrates a perspective view of an embodiment
including at least one frozen piercing implement device.
FIG. 128 A illustrates a cross-sectional view of an embodiment
including at least one frozen piercing implement.
FIG. 128 B illustrates a perspective view of a plurality of frozen
piercing implements, according to an illustrated embodiment.
FIG. 128 C illustrates a perspective view of an embodiment of at
least one frozen piercing implement device.
FIG. 128 D illustrates a perspective view of an embodiment of at
least one frozen piercing implement device.
FIG. 129 A illustrates a cross-sectional view of an embodiment of
at least one frozen piercing implement.
FIG. 129 B illustrates a cross-sectional view of an embodiment of
at least one frozen piercing implement.
FIG. 130 A illustrates a cross-sectional view of an embodiment of
at least one frozen piercing implement device.
FIG. 130 B illustrates a cross-sectional view of an embodiment of
at least one frozen piercing implement device.
FIG. 131 A illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 B illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 C illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 D illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 E illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 F illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 G illustrates a perspective view of an embodiment
including a plurality of frozen piercing implements, including at
least one frozen piercing implement device.
FIG. 131 H illustrates a perspective view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
FIG. 132 illustrates a perspective view of an embodiment including
at least one frozen piercing implement device, optionally including
a plurality of frozen piercing implements.
FIG. 133 A illustrates a cross-sectional view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
FIG. 133 B illustrates a cross-sectional view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
FIG. 134 A illustrates a cross-sectional view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
FIG. 134 B illustrates a cross-sectional view of an embodiment
including at least one frozen piercing implement device, optionally
including a plurality of frozen piercing implements.
FIG. 135 illustrates a partial view of a method 13500, in which
embodiments may be implemented.
FIG. 136 illustrates a partial view of the method of FIG. 135, in
which embodiments may be implemented.
FIG. 137 illustrates a partial view of the method of FIG. 135, in
which embodiments may be implemented.
FIG. 138 illustrates a partial view of the method of FIG. 135, in
which embodiments may be implemented.
FIG. 139 illustrates a partial view of the method of FIG. 135, in
which embodiments may be implemented.
FIG. 140 A-C illustrates a cross-sectional view of an example of an
embodiment of a frozen piercing implement device.
FIG. 141 illustrates a partial view of a method 14100, in which
embodiments may be implemented.
FIG. 142 illustrates a partial view of the method of FIG. 141, in
which embodiments may be implemented.
FIG. 143 illustrates a partial view of the method of FIG. 141, in
which embodiments may be implemented.
FIG. 144 illustrates a partial view of the method of FIG. 141, in
which embodiments may be implemented.
FIG. 145 illustrates a partial view of the method of FIG. 141, in
which embodiments may be implemented.
FIG. 146 illustrates a partial view of the method of FIG. 141, in
which embodiments may be implemented.
FIG. 147 illustrates a partial view of the method of FIG. 141, in
which embodiments may be implemented.
FIG. 148 illustrates a partial view of a method 14800, in which
embodiments may be implemented.
FIG. 149 illustrates a partial view of the method of FIG. 148, in
which embodiments may be implemented.
FIG. 150 illustrates a partial view of the method of FIG. 148, in
which embodiments may be implemented.
FIG. 151 illustrates a partial view of a method 15100, in which
embodiments may be implemented.
FIG. 152 illustrates a partial view of the method of FIG. 151, in
which embodiments may be implemented.
FIG. 153 illustrates a partial view of the method of FIG. 151, in
which embodiments may be implemented.
FIG. 154 illustrates a partial view of the method of FIG. 151, in
which embodiments may be implemented.
FIG. 155 illustrates a partial view of the method of FIG. 151, in
which embodiments may be implemented.
FIG. 156 illustrates a partial view of the method of FIG. 151, in
which embodiments may be implemented.
FIG. 157 illustrates a partial view of the method of FIG. 151, in
which embodiments may be implemented.
FIG. 158 illustrates a partial view of a method 15800, in which
embodiments may be implemented.
FIG. 159 illustrates a partial view of the method of FIG. 158, in
which embodiments may be implemented.
FIG. 160 illustrates a partial view of the method of FIG. 158, in
which embodiments may be implemented.
FIG. 161 illustrates a partial view of the method of FIG. 158, in
which embodiments may be implemented.
FIG. 162 illustrates a partial view of a method 16200, in which
embodiments may be implemented.
FIG. 163 illustrates a partial view of a system 16300, in which
embodiments may be implemented.
FIG. 164 illustrates partial view of the system of FIG. 163, in
which embodiments may be implemented.
FIG. 165 illustrates a partial view of the system of FIG. 163, in
which embodiments may be implemented.
FIG. 166 illustrates a partial view of the system of FIG. 163, in
which embodiments may be implemented.
FIG. 167 illustrates a partial view of a system 16700, in which
embodiments may be implemented.
FIG. 168 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 169 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 170 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 171 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 172 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 173 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 174 illustrates a partial view of the system of FIG. 167, in
which embodiments may be implemented.
FIG. 175 illustrates a partial view of a system 17500, in which
embodiments may be implemented.
FIG. 176 illustrates a partial view of the system of FIG. 175, in
which embodiments may be implemented.
FIG. 177 illustrates a partial view of the system of FIG. 175, in
which embodiments may be implemented.
FIG. 178 illustrates a partial view of the system of FIG. 175, in
which embodiments may be implemented.
FIG. 179 illustrates a partial view of the system of FIG. 175, in
which embodiments may be implemented.
FIG. 180 illustrates a partial view of the system of FIG. 175, in
which embodiments may be implemented.
FIG. 181 illustrates a partial view of the system FIG. 175, in
which embodiments may be implemented.
FIG. 182 illustrates a partial view of a system 18200, in which
embodiments may be implemented.
FIG. 183 illustrates a partial view of the system of FIG. 182, in
which embodiments may be implemented.
FIG. 184 illustrates a partial view of the system of FIG. 182, in
which embodiments may be implemented.
FIG. 185 illustrates a partial view of the system of FIG. 182, in
which embodiments may be implemented.
FIG. 186 illustrates a partial view of a system 18600, in which
embodiments may be implemented.
FIG. 187 illustrates a partial view of the system of FIG. 186, in
which embodiments may be implemented.
FIG. 188 illustrates a partial view of the system of FIG. 186, in
which embodiments may be implemented.
FIG. 189 illustrates a partial view of the system of FIG. 186, in
which embodiments may be implemented.
FIG. 190 illustrates a partial view of a system 19000, in which
embodiments may be implemented.
FIG. 191 illustrates a partial view of the system of FIG. 190, in
which embodiments may be implemented.
FIG. 192 illustrates a partial view of the system of FIG. 190, in
which embodiments may be implemented.
FIG. 193 illustrates a partial view of a computer program product
19300, in which embodiments may be implemented.
FIG. 194 illustrates a partial view of the computer program product
of FIG. 193, in which embodiments may be implemented.
FIG. 195 illustrates a partial view of the computer program product
of FIG. 193, in which embodiments may be implemented.
FIG. 196 illustrates a partial view of a system 19600, in which
embodiments may be implemented.
FIG. 197 illustrates a partial view of the system of FIG. 196, in
which embodiments may be implemented.
FIG. 198 illustrates a partial view of the system of FIG. 196, in
which embodiments may be implemented.
FIG. 199 illustrates a partial view of a system 19900, in which
embodiments may be implemented.
FIG. 200 illustrates a partial view of the system of FIG. 199, in
which embodiments may be implemented.
FIG. 201 illustrates a partial view of a system 20100, in which
embodiments may be implemented.
FIG. 202 illustrates a partial view of the system of FIG. 201, in
which embodiments may be implemented.
FIG. 203 illustrates a partial view of the system of FIG. 201, in
which embodiments may be implemented.
FIG. 204 illustrates a partial view of the system of FIG. 201, in
which embodiments may be implemented.
FIG. 205 illustrates a partial view of a system 20500, in which
embodiments may be implemented.
FIG. 206 illustrates a partial view of the system of FIG. 205, in
which embodiments may be implemented.
FIG. 207 illustrates a partial view of the system of FIG. 205, in
which embodiments may be implemented.
FIG. 208 illustrates a partial view of the system of FIG. 205, in
which embodiments may be implemented.
FIG. 209 illustrates a partial view of a computer program product
20900, in which embodiments may be implemented.
FIG. 210 illustrates a partial view of the computer program product
of FIG. 209, in which embodiments may be implemented.
FIG. 211 illustrates a partial view of the computer program product
of FIG. 209, in which embodiments may be implemented.
FIG. 212 illustrates a partial view of a system 21200, in which
embodiments may be implemented.
FIG. 213 illustrates a partial view of the system of FIG. 212, in
which embodiments may be implemented.
FIG. 214 illustrates a partial view of the system of FIG. 212, in
which embodiments may be implemented.
FIG. 215 illustrates a partial view of a system 21500, in which
embodiments may be implemented.
FIG. 216 illustrates a partial view of the system of FIG. 215, in
which embodiments may be implemented.
FIG. 217 illustrates a partial view of the system of FIG. 215, in
which embodiments may be implemented.
FIG. 218 illustrates a partial view of the system of FIG. 215, in
which embodiments may be implemented.
DETAILED DESCRIPTION
In the following detailed description, reference is made to the
accompanying drawings, which form a part hereof. In the drawings,
similar symbols typically identify similar components, unless
context dictates otherwise. The illustrative embodiments described
in the detailed description, drawings, and claims are not meant to
be limiting. Other embodiments can be utilized, and other changes
can be made, without departing from the spirit or scope of the
subject matter presented here.
In one embodiment, at least one frozen particle composition
(including therapeutic compositions), device, system, product,
machine, or method disclosed herein relates to making,
administering, or utilizing one or more frozen particle
compositions for various purposes.
Frozen Particles
In one embodiment, the one or more frozen particle compositions,
frozen piercing implements, or frozen piercing implement devices
include one or more frozen particles and optionally, at least one
other agent. In one embodiment, the at least one agent includes at
least one of a therapeutic agent, reinforcement agent, abrasive,
biological remodeling agent, explosive material, or adhesive agent.
In one embodiment, the frozen particle composition or frozen
piercing implement (or device) includes at least one material that
modulates the rate of diffusion or degradation of the at least one
agent. In one embodiment, the at least one material reduces the
rate of diffusion or degradation of the at least one agent.
In one embodiment, the at least one agent includes or is
substantially in the form of at least one of an organic or
inorganic small molecule, clathrate or caged compound, protocell,
coacervate, microsphere, Janus particle, proteinoid, laminate,
helical rod, liposome, macroscopic tube, niosome, sphingosome,
toroid, vesicular tube, vesicle, small unilamellar vesicle, large
unilamellar vesicle, large multilamellar vesicle, multivesicular
vesicle, lipid layer, lipid bilayer, micelle, organelle, cell,
membrane, nucleic acid, peptide, polypeptide, protein,
glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) include one or more frozen
particles made up of at least one frozen constituent. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) include one or more frozen
particles including a single frozen constituent. In one embodiment,
the one or more frozen particles include multiple frozen
constituents. In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements (or devices) include
frozen solute particles, and optionally, at least one agent. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements (or devices) include non-hydrogen oxide frozen
solute particles, and optionally, at least one agent. In one
embodiment, the one or more frozen particle compostions, or frozen
piercing implements (or devices) include frozen solvent particles,
and optionally, at least one agent. In one embodiment, the one or
more frozen particle compositions, or frozen piercing implements
(or devices) include non-hydrogen oxide frozen solvent particles
and optionally, at least one agent. In one embodiment, the one or
more frozen particle compositions, or frozen piercing implements
(or devices) include frozen solution particles, and optionally, at
least one agent. In one embodiment, a frozen particle composition,
or frozen piercing implement (or device) includes one or more
frozen solution particles and at least one agent; wherein the
frozen particle composition is in at least one crystalline or
amorphous phase.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements (or devices) include frozen particles of
at least one component that is in a gaseous state at or above
physiological conditions, which include but are not limited to
approximately 0.25 bar, approximately 0.5 bar, approximately 1.0
bar, approximately 5.0 bar, approximately 10.0 bar, approximately
25 bar, approximately 50 bar, approximately 100 bar, approximately
200 bar, or approximately 500 bar pressure; and at or above
approximately 10.degree. C., approximately 15.degree. C.,
approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 35.degree. C.,
approximately 37.degree. C., approximately 40.degree. C.,
approximately 45.degree. C., approximately 50.degree. C.
In one embodiment, the frozen particle composition, or frozen
piercing implement (or device) includes one or more frozen
particles including at least one of hydrogen oxide, helium, neon,
krypton, argon, xenon, nitrogen, chlorine, bromine, methane,
oxygen, air, carbon dioxide, polyethylene glycol, acetone, ethyl
acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
tetrahydrofuran, acetronitrile, acetic acid, n-butanol,
isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, methane,
diethyl ether, or any solution, suspension, mixture, or colloid
including one or more thereof.
In one embodiment, the frozen particle composition, or frozen
piercing implement (or device) includes one or more frozen solution
particles, optionally including at least one agent; wherein the one
or more frozen solution particles have at least one major dimension
of approximately one centimeter or less, approximately one
millimeter or less, approximately one micrometer or less,
approximately one nanometer or less, or any value therebetween.
In one embodiment, at least one of the constituents of the one or
more frozen particle compositions or frozen piercing implements (or
devices) is frozen. In one embodiment, all of the constituents of
the one or more frozen particle compositions or frozen piercing
implements (or devices) are frozen. In one embodiment, the one or
more frozen particle compositions, or frozen piercing implements
(or devices) have at least one major dimension of approximately one
decimeter or less, approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer or less, approximately one
picometer or less, or any value therebetween.
In one embodiment, a plurality of frozen particle compositions or
frozen piercing implements (or devices) is delivered or
administered, and the plurality includes at least two subsets of
frozen particle compositions or frozen piercing implements which
can be differentiated based on size. In one embodiment, a plurality
of frozen particle compositions or frozen piercing implements
includes at least one subset of frozen particle compositions or
frozen piercing implements that have at least one major dimension
of approximately ten micrometers or less. In one embodiment, the at
least one major dimension of the one or more frozen particle
compositions or frozen piercing implements (or devices) includes at
least one of radius, diameter, length, width, height, or
perimeter.
As described herein, in one embodiment, the one or more frozen
particle compositions or frozen piercing implements approximate the
shape of at least one of a sphere, bullet, flechette, cone, needle,
arrow, spear, diamond, pyramid, cylinder, mini ball, shuttlecock,
spiral, helical, bell, pear, crystal, cube, spheroid, tetrahedron,
crescent, or high aspect ratio shape. The size, shape, weight, or
density, as well as other physical parameters of the one or more
frozen particle compositions or frozen piercing implements can be
adjusted according to a particular parameter for making or
administering the frozen particle composition, or frozen piercing
implement, or desired goal in utilizing the frozen particle
composition(s) or frozen piercing implement(s). In one embodiment,
the one or more frozen particle compositions or frozen piercing
implements include a plurality of frozen particles that are
approximately uniform with regard to size, shape, weight, or
density. In one embodiment, the one or more frozen particle
compositions or frozen piercing implements include an array of
different sizes, shapes, weights, or densities.
In one embodiment, the frozen particle composition, or frozen
piercing implements is substantially in the form of a hatchet, saw,
rotary device, fork, sciber, graver, spade, screw, pin, needle,
blade, knife, razor, scissors, tweezers, scalpel, or other tool. In
one embodiment, the frozen particle composition, or frozen piercing
implement includes at least one microneedle, micropin, nanoneedle,
or nanopin. In one embodiment, the frozen particle composition, or
frozen piercing implements includes means for piercing, stitching,
extracting material, or administering at least one agent to at
least one substrate.
In one embodiment, the one or more frozen particle compositions or
frozen piercing implements are substantially solid at about
30.degree. C., about 20.degree. C., about 10.degree. C., about
5.degree. C., about 0.degree. C., about -10.degree. C. about
-20.degree. C., about -30.degree. C., about -40.degree. C., about
-50.degree. C., about -60.degree. C., about -70.degree. C., about
-75.degree. C., about -80.degree. C., about -85.degree. C., about
-90.degree. C., about -95.degree. C., about -100.degree. C., about
-120.degree. C., about -150.degree. C., about -180.degree. C.,
about -200.degree. C., about -220.degree. C., about -250.degree.
C., or any temperature less than or therebetween. In one
embodiment, a frozen piercing implement is substantially solid if
it is approximately 1%, approximately 5%, approximately 10%
approximately 20%, approximately 30%, approximately 40%,
approximately 50%, approximately 60%, approximately 70%,
approximately 80%, approximately 90%, approximately 99%,
approximately 100% solid, or any value therebetween.
In one embodiment, the frozen particle composition or frozen
piercing implement (or device) includes at least one of a solid,
liquid, or gas. In one embodiment, the frozen particle composition,
or frozen piercing implement (or device) includes at least one of a
frozen liquid, or frozen gas. In one embodiment, the frozen
particle composition or frozen piercing implement (or device)
includes at least one pharmaceutically acceptable carrier or
excipient. In one embodiment, the frozen particle composition, or
frozen piercing implement (or device) is formulated to be
administered by one or more of topical administration, oral
administration, enteral administration, mucosal administration,
percutaneous administration, or parenteral administration. In one
embodiment, parenteral administration includes at least one of
intravenous administration, intra-arterial administration,
intracardiac administration, subcutaneous administration,
intraperitioneal administration, or intramuscular administration.
In one embodiment, the frozen particle composition, or frozen
piercing implement (or device) is formulated to be administered by
high velocity impact. In one embodiment, the frozen particle
composition, or frozen piercing implement (or device) is formulated
to be administered by one or more devices.
In one embodiment, the at least one frozen particle composition or
frozen piercing impelement at least partially melts during
administration, or upon contact with the substrate (e.g.,
biological cell, tissue, or organ). For example, the frozen
components of the at least one frozen particle composition or
frozen piercing implement will melt or vaporize as a thermal
transfer occurs from the environment or substrate (e.g., biological
cell, tissue, organ, structure, or device) to the composition or
implement. In one example, the heat of a subject's body to which
the frozen particle composition or implement is administered at
least partially melts or vaporizes at least one component of the
composition or implement. In one embodiment, at least part of the
composition or implement does not melt or vaporize (e.g., magnetic
particles, therapeutic agent, sensor, etc.). In one embodiment, the
frozen particle composition or frozen piercing implement acts as a
vehicle for delivering at least one agent (therapeutic agent,
adhesive agent, biological remodeling agent, etc.) or article
(e.g., sensor, detection material, etc.) wherein the vehicle
dissipates upon administration.
As described herein, in one embodiment, the substrate is cooled
prior to, during, or subsequent to administration of the at least
one frozen particle composition or frozen piercing implement, which
reduces the thermal transfer and allows for a slower melting or
evaporation process to occur. In one embodiment, all of the
constituents of the frozen particle composition or frozen piercing
implement are frozen. In one embodiment, at least one constituent
of the frozen particle composition or frozen piercing implement is
not frozen (e.g., magnetic particle, adhesive agent, sensor,
etc.).
In one embodiment, the frozen particle composition, or frozen
piercing implement (or device) includes one or more of a
suspension, mixture, solution, sol, clathrate, colloid, emulsion,
microemulsion, aerosol, ointment, capsule, powder, tablet,
suppository, cream, device, paste, resin, liniment, lotion, ampule,
elixir, spray, syrup, tincture, detection material, polymer,
biopolymer, buffer, adjuvant, diluent, lubricant, disintegration
agent, suspending agent, solvent, light-emitting agent,
colorimetric agent, glidant, anti-adherent, anti-static agent,
surfactant, plasticizer, emulsifying agent, flavor, gum, sweetener,
coating, binder, filler, compression aid, encapsulation aid,
preservative, granulation agent, spheronization agent, stabilizer,
adhesive, pigment, sorbent, nanoparticle, or gel.
In one embodiment, the one or more frozen particles include one or
more frozen hydrogen oxide particles. In one embodiment, the frozen
particle composition, or frozen piercing implement (or device)
includes one or more frozen particles, wherein the frozen hydrogen
oxide particle is in one or more phases including at least one of
amorphous solid water, low density amorphous ice, high density
amorphous ice, very high density amorphous ice, clathrate ice,
hyperquenched glassy water, ice Ic, ice Ih, ice II, ice III, ice
IV, ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice
XII, ice XIII, ice XIV, or ice XV.
In one embodiment, the one or more frozen particle compositions,
frozen piercing implements (or devices) include frozen hydrogen
oxide particles. Frozen hydrogen oxide, or typical water ice,
exists in several non-crystalline forms. Each of these forms has
specific physical characteristics such as density and vibrational
spectra. Some examples of frozen hydrogen oxide phase
transformations are shown in FIG. 1. (See e.g., Chaplin, the
worldwide web at lsbu.ac.uk/water; Ivanov et al., Russian J. Gen.
Chem. vol. 75, pp. 1851-1856 (2005), each of which is incorporated
herein by reference).
Hydrogen oxide (water) has many frozen phases (ices), including
crystalline and non-crystalline phases. The crystalline phases
generally have the common structure of having hydrogen bonds to
four neighboring water molecules, such as two hydrogen atoms near
each oxygen atom. Structural data on the known frozen hydrogen
oxide polymorphs are shown in Table I, with two known phases of ice
XI. (See, e.g., Chaplin, Ibid; and Zheligovskaya, et al., Russian
Chem. Rev.75, pp. 57-76, 2006, each of which is incorporated herein
by reference).
TABLE-US-00001 TABLE I Structural Data on the Ice Polymorphs
Dielectric Density, constant, Ice polymorph g/cm.sup.3 Protons
Crystal Symmetry .epsilon..sub.S Notes Hexagonal ice, Ih 0.92
disordered Hexagonal One C.sub.6 97.5 Cubic ice, Ic 0.92 disordered
Cubic four C.sub.3 LDA, Ia 0.94 disordered Non- As prepared,
crystalline can be mixtures of several types HAD 1.17 disordered
Non- As prepared, crystalline can be mixtures of several types VHDA
1.25 disordered Non- crystalline II 1.17 ordered Rhombohedral One
C.sub.3 3.66 III 1.14 disordered Tetragonal One C.sub.4 117 protons
can be partially ordered IV 1.27 disordered Rhombohedral One
C.sub.3 metastable in ice V phase space V 1.23 disordered
Monoclinic One C.sub.2 144 protons can be partially ordered VI 1.31
disordered Tetragonal One C.sub.4 193 protons can be partly ordered
VII 1.50 disordered Cubic four C.sub.3 150 two interpenetrating ice
Ic frameworks VIII 1.46 ordered Tetragonal One C.sub.4 4 low
temperature form of ice VII IX 1.16 ordered Tetragonal One C.sub.4
3.74 low temperature form of ice III, metastable in ice II space X
2.51 symmetric Cubic four C.sub.3 symmetric proton, form of ice VII
XI 0.92 ordered Orthorhombic three C.sub.2 low temperature form of
ice Ih XI >2.51 symmetric Hexagonal distorted Found in close
packed simulations only XII 1.29 disordered Tetragonal One C.sub.4
metastable in ice V phase space XIII 1.23 ordered Monoclinic One
C.sub.2 ordered form of ice V phase XIV 1.29 mostly Orthorhombic
One C.sub.4 ordered form of ordered ice XII phase XV 1.31 (?)
ordered ? ? ordered form of ice VI phase
Cooling liquid hydrogen oxide below its standard freezing point
typically results in the formation of frozen hexagonal ice.
However, if the hydrogen oxide is pure and cooled slowly, the
liquid hydrogen oxide can be supercooled to approximately
-42.degree. C. Amorphous solids harden without crystallizing, such
that if hydrogen oxide is cooled rapidly it results in formation of
a glass-like state, for example, hyperquenched glassy water. (See
e.g., Debenedetti, J. Phys. Condens. Matter, vol. 15, pp.
R1669-R1726 (2003) which is incorporated herein by reference.)
Generally, hyperquenched glassy water is formed by rapidly spraying
a fine mist of micrometer-sized hydrogen oxide droplets into very
cold liquefied gas, such as propane. Alternatively, a fine mist of
hydrogen oxide can be sprayed onto a very cold frozen cell or
tissue, for example, at or below approximately -193.degree. C.
Hyperquenched glassy water may also be formed by cooling capillary
tubes containing bulk liquid water (.about.100 .mu.m diameter) with
liquid helium, for example, at approximately -269.degree. C. In one
embodiment, the frozen particle composition includes a constitutent
in a superglass state, or supersolid. For example, solid helium
includes a supersolid, or a superglass amorphous solid. See, for
example, Hunt, et al., Science, vol. 324, pp. 632-635 (2009), which
is incorporated herein by reference.
As shown in FIGS. 1-4, hydrogen oxide attains various structures
and phases depending upon the temperature or pressure of the
environment. As indicated in FIG. 1, for example, hydrogen oxide
ice Ic is derived from high density amorphous water or deeply
supercooled liquid water, when put under low temperature or higher
pressure. Likewise, as indicated in FIG. 2, the hydrogen oxide has
a greater density as a liquid than as a solid under ambient
conditions (ice Ih). However, at increasing pressure, at least ice
stages III, V, VI, and VII exhibit a greater density than liquid
hydrogen oxide. FIG. 3 indicates the phase diagram for hydrogen
oxide based on pressure and temperature variance, while FIG. 4
shows the specific sub-categories of hydrogen oxide based on
physical properties, such as structure and density, among others,
as the temperature and pressure vary.
Similarly, amorphous solid water is formed from the slow deposition
of hydrogen oxide vapor on a cold metal crystal surface (for
example, at less than approximately 2 nm/s), below the temperature
of approximately -153.degree. C. Amorphous solid water is a viscous
semi-solid material that has a density of approximately 0.94
g/cm.sup.3 and harbors gaps and spaces in its structure, as well as
reactive hydrogen bonds. These structures are removed by annealing
under vacuum pressure, which allows the material to convert to a
high density glassy water or low density amorphous ice, depending
on the temperature. Typically, high density glassy water, which has
a density of approximately 1.1 g/cm.sup.3, is formed by vapor
deposition at approximately -263.degree. C.
Low-density amorphous (LDA) ice also occurs from heating
high-density amorphous (HDA) ice to just above approximately
-153.degree. C. at atmospheric pressure, and transforms to cubic
ice at approximately -113.degree. C. to -123.degree. C. Low-density
amorphous ice is also prepared by submitting low-pressure phases
(Ih, Ic, XI, etc.) to high pressure (e.g., approximately 1.0 GPa)
at low temperatures (e.g., below approximately -148.degree.
C.).
Very-high density amorphous (VHDA) ice is a viscous water state
with a density of approximately 1.25 g/cm.sup.3, and is prepared by
heating high-density amorphous ice to just above approximately
-113.degree. C. and approximate pressure of 1.15 GPa. When
very-high density amorphous ice is heated at different pressures
between, e.g., 0.3 and 2 GPa, it re-crystallizes into only the
proton disordered ices III, IV, V, XII, VI and VII in order of
increasing pressure, but does not typically re-crystallize into the
proton ordered phases (e.g., ice II).
Typically, the density of liquid water increases with increased
pressure. When liquid water approaches the critical point in the
liquid-vapor phase, water enters a supercritical phase where it
exists as small but liquid-like hydrogen-bonded clusters dispersed
within a gas-like phase and its physical properties vary according
to changing density. Supercritical water is an excellent solvent
for non-polar molecules, due to its low dielectric constant and
poor hydrogen bonding. Due to these same properties, supercritical
water is typically not a good solvent for electrolytes, which tend
to form ionic bonds.
As indicated in FIG. 2, hexagonal ice is less dense than liquid
water, whereas the other ice phases are all denser and phase
changes occur near the liquid and solid densities (See e.g.,
Loerting et al., J. Phys.: Condens. Matter vol. 18, R919-R977
(2006), which is incorporated herein by reference). Liquid water
density varies with change in temperature or pressure, whereas the
density of amorphous ice varies only with change in pressure, but
not temperature.
Hydrogen oxide has a high heat of vaporization (approximately 40.7
kJ/mol), and a high heat of sublimation (approximately 51.059
kJ/mol at 0.degree. C.), which allows for the frozen particle
compositions to remain intact for a short time period during which
the particles are delivered to one or more cells or tissues. These
properties further enable the frozen particle compositions, or
frozen piercing implements to serve as particles for delivery of at
least one therapeutic composition to one or more cells or
tissues.
Frozen particle compositions, or frozen piercing implements may
include a "solid," such as true solids, semi-solids, and viscous
fluid, such as gels, polymers, hydrogels, or sols. Frozen particle
compositions, or frozen piercing implements including one or more
frozen particles may include particles that are at least partially
frozen, or are entirely frozen. Frozen particle compositions, or
frozen piercing implements including one or more frozen particles
may include one or more subset groups of one or more particles,
some of which are entirely frozen and some of which are at least
partially frozen. For example, a frozen particle composition may be
at least about 1% frozen, about 5% frozen, about 10% frozen, about
20% frozen, about 30% frozen, about 40% frozen, about 50% frozen,
about 60% frozen, about 70% frozen, about 80% frozen, about 90%
frozen, about 95% frozen, about 98% frozen, about 99% frozen, about
100% frozen, or any value there between.
In one embodiment, frozen particle compositions, or frozen piercing
implements may include multiple different constitutions, wherein a
group of frozen particle compositions, or frozen piercing
implements includes at least one subset of multiple frozen
particles, wherein each frozen particle has an individual
therapeutic agent, adhesive agent, biological remodeling agent,
abrasive, explosive material, reinforcement agent, other agent, a
common constitution, or unique constitution. The group of frozen
particle compositions, or frozen piercing implements may also
include at least one subset of multiple frozen particles, wherein
each frozen particle includes multiple agents.
A particular plurality of frozen particle compositions, or frozen
piercing implements may include multiple frozen particles where
various multiple agents are associated with a single particle.
Likewise, a particular plurality of frozen particle compositions,
or frozen piercing implements may include various multiple agents,
where each individual agent is associated with a single frozen
particle. In one embodiment, a plurality of frozen particle
compositions, or frozen piercing implements includes any number of
subsets of frozen particles associated with a particular agent, or
other constituent. During the course of any particular method
described herein, one or more plurality of frozen particle
compositions, or frozen piercing implements, or any particular
subset thereof, can be administered in a single treatment or in
multiple treatments. A frozen particle composition or frozen
piercing implement including at least one therapeutic agent may be
referred to as a "therapeutic composition" or "frozen particle
therapeutic composition" herein.
In certain instances, the one or more frozen particle compositions,
or frozen piercing implements are utilized at a very low
temperature, which may increase the degree of penetration of the
one or more particles or the one or more compositions or implements
for a biological tissue. In certain instances, the one or more
frozen particle compositions, or frozen piercing implements are
utilized at higher temperatures, depending on the freezing
temperature of the constituents of the one or more particles, the
goals of administration or treatment, or other factors. For
example, the freezing point of nitrogen is approximately
-210.degree. C., whereas the freezing point of dimethyl sulfoxide
(DMSO) is approximately 18.45.degree. C. In one embodiment, the one
or more frozen particle compositions, or frozen piercing implements
are utilized at room temperature, or physiological temperature.
Hydrogen oxide becomes more viscous as the temperature is decreased
to below approximately 33.degree. C., or the pressure is increased.
Ice Ic is generally formed by condensation of water vapor, at
ambient pressure and low temperatures (less than approximately
-80.degree. C.), or below approximately -38.degree. C. as a mist.
(See e.g., Murray et al., Phys. Chem. Chem. Phys. Vol. 8, pp.
186-192 (2006), which is incorporated herein by reference). Ice Ic
is also prepared by reducing the pressure on high-pressure hydrogen
oxide ice at approximately -196.degree. C. It can be the preferred
phase for ice formed from hydrogen oxide droplets smaller than
about 15 nm in radius, particularly at low temperatures (e.g.,
-113.degree. C. to -53.degree. C.). (See e.g., Johari, J. Chem.
Phys. vol. 122 pp. 194504 (2005); Zhang, et al., Chem. Phys. Lett.
vol. 421, pp. 251-255 (2006), each of which is incorporated herein
by reference).
Ice Ih constitutes a large portion of naturally-occurring snow and
ice. Since hexagonal ice exhibits changes in the hydrogen bonding,
ice Ih shows anomalous reduction in thermal conductivity with
increasing pressure (as does cubic ice and low-density amorphous
ice). (See e.g., Andersson et al., Phys. Rev. B vol. 65 pp.
140201.1-14201.4 (2002), which is incorporated herein by
reference).
Ice II maintains a general rhombohedral unit shape, similar to ice
I. The density of ice II is approximately 1.17 g/cm.sup.3. Ice III
maintains a general tetragonal unit shape, with a density of
approximately 1.14 g/cm.sup.3. Ice VI also maintains a general
tetragonal unit shape, with a density of approximately 1.31
g/cm.sup.3. Ice VII is primarily composed of multiple intercalating
ice Ic lattices, and has a density of approximately 1.66
g/cm.sup.3.
Some non-limiting examples of materials that are included in one or
more compositions, or implements described herein include, but are
not limited to, liquid nitrogen, which is nontoxic and inert, with
a freezing point at 1 atm pressure of approximately -210.degree. C.
Liquid helium is nontoxic and inert, with a freezing point at 367
psi of approximately -272.2.degree. C. Liquid argon is nontoxic and
inert with a freezing point at 1 atm pressure of approximately
-189.4.degree. C. Liquid neon has a freezing point of approximately
-245.95.degree. C., while liquid xenon has a freezing point of
approximately -111.9.degree. C. The freezing point of liquid
dimethyl sulfoxide (DMSO) is approximately 18.45.degree. C., and
water or other co-solvents can decrease the freezing point. The
freezing point of lactated Ringer's solution is approximately
-45.degree. C. These and other materials can be utilized as
described herein either alone, or in combination with other
materials.
In one embodiment, at least one frozen particle composition, or
frozen piercing implement, is made or maintained by utilizing a
magnetic time-averaged orbiting potential trap. See, for example,
Han et al., Phys. Rev. vol. 57, pp. R4114-4117 (1998), which is
incorporated herein by reference. In one embodiment, the at least
one frozen particle composition includes one or more Bose-Einstein
condensation of a dilute atomic gas. Id.
In one embodiment, the frozen particle composition, or frozen
piercing implements includes a clathrate. Clathrate ice forms from
water or other liquids, and contains small amounts of non-polar
molecules (generally gases) under moderate pressure of a few MPa,
and temperatures close to 0.degree. C. Clathrate structures can
vary, but generally allow a minimum amount of small molecules to
fit into and stabilize gaps without forming covalent or hydrogen
bonds with the hydrogen oxide molecules. Certain clathrates are
formed at the interface of the liquid phase, under atmospheric
pressure. Clathrates include but are not limited to the structural
forms of sI, sII, and sh. In certain instances, noble gases can be
used to form clathrate compounds with hydrogen oxide or other
molecules. Noble gases generally have low polarizability, and tend
to be spherically symmetrical, which allows for solubility with the
hydrogen oxide cage. In addition, the solubility of the noble gases
increases considerably as the temperature is lowered.
The solubility properties of particular noble gases as clathrates
with hydrogen oxide are shown in Table IV. (See e.g., Dec et al.,
J. Solution Chem. vol. 14, pp. 417-429 (1985); Ivanov, et al., J.
Struct. Chem. vol. 46, pp. 253-263 (2005); Fernandez-Prini, et al.,
Elsvier, pp. 73-98 (2004); Ivanov, et al., Russian J. Gen. Chem.
vol. 75, pp. 1851-1856 (2005), each of which is incorporated herein
by reference.)
TABLE-US-00002 TABLE IV Solubility Properties of the Noble Gases
Property He Ne Ar Kr Xe Rn Atomic number 2 10 18 36 54 86 Atomic
radius, .ANG. 1.08 1.21 1.64 1.78 1.96 2.11 .DELTA.G.degree. of
solution in H.sub.2O at 25.degree. C., kJ/mol 29.41 29.03 26.25
24.80 23.42 .DELTA.H.degree. of solution in H.sub.2O at 25.degree.
C., kJ/mol -0.59 -3.80 -11.98 -15.29 -18.99 .DELTA.S.degree. of
solution in H.sub.2O at 25.degree. C., J/molK -100.6 -110.1 -128.2
-134.5 -142.2 Solubility, mM, 5.degree. C., 101,325 Pa H.sub.2O
0.41 0.53 2.11 4.20 8.21 18.83 D.sub.2O 0.49 0.61 2.38 4.61 8.91
20.41 Solubility minima, .degree. C. H.sub.2O 30 50 90 108 110
D.sub.2O 53 53 98 108 116
In one embodiment, the frozen particle composition, or frozen
piercing implements includes at least two frozen particles that are
joined. In one embodiment, the at least two frozen particles are
joined by at least one agent. In one embodiment, the at least two
frozen particles are joined by at least one cavity or compartment.
In one embodiment, the frozen particle composition, or frozen
piercing implement includes a cluster of three or more frozen
particles that are joined. In one embodiment, the cluster of three
or more frozen particles is joined by at least one agent. In one
embodiment, the cluster of three or more frozen particle is joined
by at least one cavity or compartment.
Cavitized or Compartmentalized Frozen Particle Compositions or
Frozen Piercing Implements
In one embodiment, the frozen particle composition, or frozen
piercing implement includes at least one frozen particle as
described herein, defining at least one cavity or compartment
configured for holding at least one agent, article or other
material. In one embodiment, the at least one cavity contains at
least one agent. In one embodiment, the frozen particle
composition, or frozen piercing implement includes at least one
frozen particle defining at least one cavity or compartment
containing at least one agent, and further including one or more
agents located outside of the at least one cavity.
In one embodiment, the frozen particle composition, or frozen
piercing implement includes at least one inlet port in fluid
communication with the at least one cavity. In one embodiment, the
frozen particle composition, or frozen piercing implement includes
at least one status indicator. In one embodiment, the at least one
status indicator indicates one or more of: content of the at least
one cavity, amount of cavity space occupied, or amount of cavity
space available. In one embodiment, the at least one status
indicator includes at least one of a sensor, a magnet, a
colorimetric substance, or a physical measuring device. In one
embodiment, the at least one status indicator measures one or more
of a change in cavity volume, a change in cavity shape, a change in
cavity temperature, a change in cavity pressure, a change in cavity
pH, a change in frozen particle density, a change in frozen
particle volume, a change in frozen particle weight, a change in
frozen particle temperature, a change in frozen particle shape, a
change in electrical field, a change in vehicle magnetic field, a
change in frozen particle pH, a change in the state of an
activatable agent of the composition, or a change in the state of
an activating factor or inactivating factor of the composition.
In one embodiment, the at least one cavity includes at least one of
a permeable, semi-permeable or impermeable partition. In one
embodiment, the at least one cavity includes at least one of at
least one means for at least partially sealing the cavity. In one
embodiment, the at least one cavity includes at least one cap,
seal, screw, door, or hinge. In one embodiment, the at least one
cavity is substantially in the form of at least one of a
space-filling curve, a depression, a helix, a cylinder, a spheroid,
a cuboid, a high aspect ratio shape, a tetrahedron, a pyramid, a
channel, or a cone.
In one embodiment, the at least one cavity differs in physical or
chemical composition from at least one other cavity of the frozen
particle. In one embodiment, the cavity or compartment is
configured to physically or chemically separate the at least one
agent from at least one other cavity of the frozen particle
composition, or frozen piercing implement. In one embodiment, the
at least one cavity or compartment is configured to physically or
chemically separate from at least one other cavity or compartment
of the frozen particle composition, or frozen piercing implement
during administration. In one embodiment the frozen particle
composition, or frozen piercing implement includes at least one
agent, and the at least one agent includes at least one agent in a
different phase state than the frozen particle composition. In one
embodiment, the at least one cavity or compartment includes at
least one of a solid, liquid, or gas. In one embodiment, the at
least one cavity or compartment includes at least one of a liquid
or gas, and at least one other cavity or compartment includes a
solid.
In one embodiment, the at least one cavity or compartment includes
at least one clathrate. In one embodiment, the at least one cavity
or compartment includes at least one matrix. In one embodiment, the
at least one cavity or compartment is an inner core cavity of at
least one frozen particle composition, or frozen piercing
implement. In one embodiment, the at least one cavity or
compartment includes an inner core region and wherein the at least
one agent is at least one of a liquid or gas. In one embodiment,
the at least one cavity or compartment is intercalated with at
least one other cavity or compartment. In one embodiment, the at
least one cavity is located at a substantially superficial or
exterior region of the one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the at least one
agent is distributed substantially uniformly within the at least
one substantially superficial or exterior region.
In one embodiment, the at least one cavity or compartment has a
higher concentration of the at least one agent than any other
cavity or compartment. In one embodiment, the at least one cavity
or compartment includes a graduated concentration of the at least
one agent. In one embodiment, the at least one cavity or
compartment includes varying levels of the at least one agent. In
one embodiment, the at least one agent is fractionated. In one
embodiment, the cavity or compartment includes one or more layers
of at least one agent. In one embodiment, the cavity or compartment
includes one or more layers of multiple agents. In one embodiment,
the at least one agent includes one or more of a pro-drug or
precursor compound. In one embodiment, the at least one agent
includes one or more time-release or extended-release formulations.
In one embodiment, the at least one agent includes an activatable
agent. In one embodiment, the at least one agent is configured to
activate upon administration of the frozen particle composition ,
or frozen piercing implement. In one embodiment, the at least one
activatable agent is configured to activate by one or more of an
enzymatic reaction, a reduction reaction, an oxidation reaction, a
reduction-oxidation reaction, a hydrolysis reaction, a dehydration
synthesis reaction, a glycosylation reaction, a phosphorylation
reaction, a dehydration reaction, a hydration reaction, a
decarboxylation reaction, a condensation reaction, a polymerization
reaction, a glycolysis reaction, a gluconeogenesis reaction, a
fermentation reaction, a photo chemical reaction, a thermal
reaction, a magnetic reaction, an electrical reaction, an
electrochemical reaction, a photolysis reaction, a photosynthetic
reaction, an esterification reaction, altering the pressure on at
least one frozen particle composition , or frozen piercing
implement, altering the content of at least one frozen particle
composition, or frozen piercing implement, altering at least one
chemical property of at least one frozen particle composition , or
frozen piercing implement, altering at least one physical property
of at least one frozen particle composition, or frozen piercing
implement , or applying at least one external stimulus to at least
one frozen particle composition, or frozen piercing implements.
In one embodiment, the at least one external stimulus includes one
or more of light, heat, electrical field, magnetic field, or
electromagnetic energy. In one embodiment, the frozen particle
composition , or frozen piercing implement further comprises at
least one activating factor or at least one inactivating factor
capable of modulating the activity of the at least one agent. In
one embodiment, the at least one activating factor or the at least
one inactivating factor forms at least part of one or more of a
lipid conjugate, carbohydrate conjugate, peptide conjugate,
polymer-lipid conjugate, fusion protein, antibody or antibody
fragment, receptor or receptor fragment, reversible inhibitor,
irreversible inhibitor, enzyme, gene repressor, gene suppressor,
microRNA, siRNA, kinase, gene activator, DNA-binding protein,
polymerase, gene promoter, gene enhancer, diamagnetic chemical,
explosive material, reactive metal, adhesive agent, abrasive,
reinforcement agent, biological remodeling agent, or therapeutic
agent.
In one embodiment, the at least one activating or inactivating
agent is configured to activate by one or more of altering the
temperature of at least one frozen particle composition, or frozen
piercing implement, altering the pressure on at least one frozen
particle composition, or frozen piercing implement, altering the
content of at least one frozen particle composition, or frozen
piercing implement, altering at least one electrical property of at
least one frozen particle composition, or frozen piercing
implement, altering at least one magnetic property of at least one
frozen particle composition, or frozen piercing implement, altering
at least one chemical property of at least one frozen particle
composition, or frozen piercing implement, altering at least one
physical property of at least one frozen particle composition, or
frozen piercing implement, or applying at least one external
stimulus to at least one frozen particle composition, or frozen
piercing implement.
In one embodiment, the at least one cavity or compartment is in
substantially in a form that is different than the remainder of the
frozen particle composition, or frozen piercing implement. In one
embodiment, the at least one cavity or compartment is substantially
in the form of at least one of an organic or inorganic small
molecule, clathrate or caged compound, protocell, coacervate,
microsphere, Janus particle, proteinoid, laminate, helical rod,
liposome, macroscopic tube, niosome, sphingosome, toroid, vesicular
tube, vesicle, small unilamellar vesicle, large unilamellar
vesicle, large multilamellar vesicle, multivesicular vesicle, lipid
layer, lipid bilayer, micelle, organelle, cell, membrane, nucleic
acid, peptide, polypeptide, protein, glycopeptide, glycolipid,
lipoprotein, sphingolipid, glycosphingolipid, glycoprotein,
peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan,
chromosome, nucleus, acid, support structure, buffer, protic
solvent, aprotic solvent, nitric oxide, nitrous oxide, nitric oxide
synthase, amino acid, micelle, polymer, copolymer, monomer,
prepolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, piloxymer, transfersome, gas,
element, contaminant, radioactive particle, hormone, microorganism,
bacteria, virus, quantum dot, contrast agent, or any part thereof.
In one embodiment, the agent includes at least one negatively
charged substance. In one embodiment, the agent includes at least
one positively charged substance.
In one embodiment, a frozen particle composition, or frozen
piercing implement comprises a frozen hydrogen oxide particle
defining two or more cavities, wherein the two or more cavities
each contain at least one agent. In one embodiment, the two or more
cavities each contain at least one different agent. In one
embodiment, the different agents are configured to combine upon
administration of the frozen particle composition, or frozen
piercing implement. In one embodiment, the different agents are
configured to react upon administration of the frozen particle
composition, or frozen piercing implement. In one embodiment, the
different agents are configured to act cooperatively or
synergistically upon administration of the frozen particle
composition, or frozen piercing implement.
In one embodiment, a frozen particle composition comprises a frozen
particle composition, or frozen piercing implement defining three
or more cavities, wherein the three or more cavities each contain
at least one agent. In one embodiment, a frozen particle
composition, or frozen piercing implement comprises a frozen
particle defining four or more cavities, five or more cavities, six
or more cavities, seven or more cavities, eight or more cavities,
or any value greater than.
Agents
In one embodiment, the frozen particle composition, or frozen
piercing implement includes at least one agent. In one embodiment,
the frozen particle provides a vehicle for the at least one agent.
In one embodiment, the frozen particle is constituted solely by the
at least one agent. In one embodiment, the agent includes at least
one nontoxic, biocompatible, bioresorbable, or biodegradable agent.
In certain instances, the one or more reinforcement agents, one or
more explosive materials, one or more abrasives, one or more
adhesive agents, or one or more therapeutic agents, or one or more
biological remodeling agents are utilized in the form of a plate,
spheroid, resin, powder, solution, flake, sheet, film, ribbon, gel,
ball, pellet, or bead. (See e.g., U.S. Pat. Nos. 5,534,584;
5,331,046; each of which is incorporated herein by reference). The
one or more materials or agents of the frozen particle
compositions, or frozen piercing implements can be in the form of a
solid, liquid, or gas. In one embodiment, one or more of the agents
are the same agent. For example, in one embodiment, the frozen
particle composition, or frozen piercing implement includes at
least one therapeutic agent that is the same as a reinforcement
agent, an adhesive agent, an abrasive, an explosive material, or a
biological remodeling agent. In one embodiment, any one single
agent is the same as any single other agent (i.e. the constitution
of an agent may be the same as another agent, or the function of an
agent may be the same as another agent).
In certain instances, at least one agent may be configured to
provide more than one function. For example, in one embodiment, the
at least one therapeutic agent and the at least one adhesive agent,
biological remodeling agent, abrasive, reinforcement agent, or
explosive material are the same agent. In one embodiment, the at
least one adhesive agent and the at least one biological remodeling
agent, therapeutic agent, abrasive, reinforcement agent, or
explosive material are the same. In one embodiment, the at least
one biological remodeling agent and the at least one adhesive
agent, therapeutic agent, abrasive, reinforcement agent, or
explosive material are the same agent. In one embodiment, the at
least one reinforcement agent and the at least one adhesive agent,
therapeutic agent, biological remodeling agent, abrasive, or
explosive material are the same. In one embodiment, the at least
one abrasive and the at least one adhesive agent, therapeutic
agent, biological remodeling agent, explosive material, or
reinforcement agent are the same. In one embodiment, the at least
one explosive material and abrasive, adhesive agent, therapeutic
agent, biological remodeling agent, or explosive material are the
same.
In one embodiment, the at least one is included as part of at least
one carrier that assists in synthesis or activation of the at least
one agent. In one embodiment, the at least one carrier encompasses
the at least one agent. In one embodiment, the carrier includes a
microbe, other cell (such as a cell from a subject or related to a
particular subject, including but not limited to a transgenic
cell). In one embodiment, the cellular carrier is included in the
one or more frozen particle compositions, or frozen piercing
implements described. In one embodiment, the carrier includes or is
substantially in the form of at least one of at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof.
In one embodiment, the at least one agent is frozen. In one
embodiment, the at least one agent is at least partially frozen. In
at least one embodiment, the frozen particle composition, or frozen
piercing implement includes one or more frozen particles and at
least one agent that is not frozen. In one embodiment, the at least
one agent includes two or more components configured to combine
upon administration of the at least one agent.
In one embodiment, the at least one agent includes one or more
inactive components. In one embodiment, the at least one agent
includes two or more components that are configured to activate
when combined. In one embodiment, the at least one agent includes
one or more components that are configured to activate when
administered. In one embodiment, at least two of the one or more
components are included in the same or different frozen particle
composition, or frozen piercing implement. In one embodiment, at
least two of the one or more components each reside in a separate
cavity of the same or a different frozen particle composition, or
frozen piercing implement. In one embodiment, at least one agent is
included as a precursor molecule.
In one embodiment, at least one agent is configured to be activated
prior to or subsequent to administration. In one embodiment, at
least one agent is configured to be activated after a prolonged
time subsequent to administration. For example, in cases where the
agent is encased or associated with a polymer or other agent that
may insulate one or more reactant or retard the explosive or
decomposition process, the release of the agent can be delayed. In
one embodiment, the frozen particle composition, or frozen piercing
implement includes at least one activatable agent. In one
embodiment, the frozen particle composition, or frozen piercing
implement includes at least one activating agent or at least one
inactivating agent, or both. In one embodiment, the at least one
agent includes two or more components configured to combine upon
deposition. In one embodiment, the at least one agent includes two
or more components configured to react upon deposition.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements including at least one agent are part of
a kit for administration, optionally to at least one substrate
(including at least one biological cell or tissue). In one
embodiment, one or more subsets of frozen particle compositions, or
frozen piercing implements include different agents or different
components of an agent and are administered in a kit or device
wherein one subset is kept separate from another subset until
administration of the frozen particle compositions, or frozen
piercing implements.
Reinforcement Agents
In one embodiment disclosed herein, one or more reinforcement
agents are included in the frozen particle composition, or frozen
piercing implement. Examples of some reinforcement agents include,
but are not limited to, polyaramid, vinylester matrix, metal
(including but not limited to gold, silver, copper, zinc, brass,
tin, bronze, gallium, sodium, potassium, tungsten, steel, iron,
carbon, aluminum, copper, platinum, tantalum, rhodium, or alloys
thereof), ceramic, fiberglass, cellulose, broad carbide, aromatic
polyamide, nylon, silk, rayon, acetate, modacrylic, olefin, acrylic
polymer or copolymer, acrylamide polymer or copolymer, polyester,
aromatic polyester, poly-lactic acid, vinyon, saran, spandex,
vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, alluvium, sand, sugar, calcite,
emery, diamond, novaculite, pumice, rouge, borazon, corundum,
zirconia alumina, silicon, silica, frozen hydrogen oxide ice, plant
matter, animal matter, or mineral matter. In one embodiment, plant
matter may include vegetable matter, nuts or nut products or pieces
(e.g., almonds), grains (e.g., oatmeal), wood (e.g., wood fibers)
or other stalk material, leaf matter, fruit matter (including pits
or seeds or parts thereof), and other plant material.
In one embodiment, one or more reinforcement agents are made by
spinning into a fiber, wire, or filament. Some non-limiting
examples of reinforcement fibers can be found at, for example, U.S.
Pat. Nos. 5,855,663; 5,652,058; KEVLAR.RTM. technical guide,
Polymer Bulletin, vol. 16, pp. 167-174 (1986), and WO12003/060002,
each of which is incorporated herein by reference.
The one or more agents are positioned on or in the one or more
frozen particle compositions depending on a given context. For
example, the positioning of one or more agents may consider the
particular goal of administering the one or more frozen particle
compositions, or frozen piercing implements, the components of the
at least one frozen particle composition, or frozen piercing
implement, or the needs or desires of a particular outcome of
treatment or administration of the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
one or more agents are located at least on the surface or beneath
the surface of the one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the one or more
agents are located within the one or more frozen particle
compositions, or frozen piercing implements.
As shown in published FIGS. 5 and 6, the strength of hydrogen oxide
ice samples increases when particular reinforcement agents are
added, according to the published studies. As indicated in
published FIG. 5, ice samples exhibit increased strength, as
measured by beam deflection as an angle of shear when reinforced
with fiberglass or kaolin. (See e.g., Kingery, Science, vol. 134,
pp. 164-168 (1960), which is incorporated herein by reference). As
indicated in FIG. 6, the maximum stress (in MPa) and strain rate
increases when particular reinforcement agents are added to the
hydrogen oxide ice samples, according to the published studies.
(See e.g., Yasui et al, Geophys. Res. Lett., vol. 35, L12206,
(2008), which is incorporated herein by reference).
Abrasives
In certain instances, the frozen particle composition or frozen
piercing implement described herein includes one or more abrasives.
The one or more abrasives may include treated or untreated
abrasives, coated abrasives, bonded abrasives, powders, aggregates,
composites, or other forms. In one embodiment, the one or more
abrasives include, but are not limited to, polyaramid, vinylester
matrix, metal, ceramic, fiberglass, cellulose, broad carbide,
aromatic polyamide, nylon, silk, rayon, acetate, modacrylic,
olefin, acrylic polymer or copolymer, acrylamide polymer or
copolymer, polyester, aromatic polyester, poly-lactic acid, vinyon,
saran, spandex, vinalon, aromatic nylon, vinylidene chloride,
modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, alluvium,
sand, sugar, calcite, emery, diamond, novaculite, pumice, rouge,
borazon, corundum, zirconia alumina, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral matter.
In one embodiment, plant matter may include vegetable matter, nuts
or nut products or pieces (e.g., almonds), grains (e.g., oatmeal),
wood (e.g., wood fibers) or other stalk material, leaf matter,
fruit matter (including pits or seeds or parts thereof), or other
plant material. In one embodiment, the abrasive includes at least
one depilatory.
Explosive Materials
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements include one or more explosive materials.
Explosive materials are typically chemically or energetically
unstable or produce a sudden expansion of the material with a
change in pressure. Such a sudden expansion of the material under
pressure changes is generally accompanied by the production of
heat. Explosive materials are generally differentiated according to
their decomposition rates. Generally, a chemical decomposition rate
of an explosive material takes about one or more years, about one
or more days, about one or more hours, about one or more minutes,
about one or more seconds, or about a fraction of a second. Certain
explosive materials are relatively stable, and may maintain their
explosive ability for some amount of time. Other explosive
materials have relatively high rates of decomposition and detonate
rapidly.
In one embodiment, frozen particle compositions, or frozen piercing
implements include one or more explosive materials that may
include, for example, at least one of a high explosive or a low
explosive. In one embodiment, the one or more explosive materials
include at least one of carbonate, carbon dioxide, nitroglycerine,
acid, base, epoxy, acrylic polymer or copolymer, acrlyamide polymer
or copolymer, urethane, hypoxyapatite, or a reactive metal. In
certain instances, the one or more explosive properties are the
result of activation of one or more explosive materials.
In certain instances, the one or more explosive properties are the
result of inherent tendencies of the frozen particle compositions,
or frozen piercing implements themselves. In certain instances, the
one or more explosive properties relate to an external event or
stimulus, such as a change in temperature or pressure. In certain
instances, the one or more explosive properties relate to a change
in light intensity. In certain instances, the one or more explosive
properties relate to a change in the composition upon
administration or contact with at least one composition, cell,
tissue, or subject. In certain instances, the one or more explosive
properties result from a temperature or pressure increase relating
to penetration of at least one cell, tissue, or subject. In certain
instances, the one or more explosive properties result from contact
with water or other moisture in a cell or tissue. In certain
instances, the one or more explosive properties result from contact
with at least one substrate. In addition to the intensity of the
one or more explosives, the one or more explosive materials may
differ with regard to the volatility, density, toxicity,
hygroscopicity, or brisance of a particular explosive material.
Explosive materials may contain at least one oxidizer that provides
fuel for certain explosive materials. In certain instances, the
oxidizer can be an oxidizing element, such as oxygen. In certain
instances, the oxidizer reacts with a reactive metal; an example of
such a compound includes reacting fine metal powder (e.g., aluminum
or magnesium) with an oxidizer (e.g., potassium chlorate or
perchlorate). Chemically pure compounds may have high decomposition
rates and lead to an explosion, including but not limited to
nitroglycerin, acetone peroxide, trinitrotoluene, nitrocellulose,
carbon, carbon monoxide, chlorine, potassium nitrate, sulfur,
nitrogen compounds (such as nitrite, nitrate, and azide), potassium
chlorate and potassium nitrate, hydrogen, ammonium nitrate,
phosphorous, dinitrogen tetroxide, or others. In one embodiment,
one or more mixtures of organic materials and oxidizers are
included. In one embodiment, one or more mixtures of reactive
metals and oxidizers or oils are included.
In one embodiment, the one or more explosive materials include
carbon dioxide gas. In one embodiment, carbon dioxide gas is
entrapped in the frozen particle composition. One method of
incorporating carbon dioxide gas into at least one frozen particle
composition, or frozen piercing implement includes liquefying the
frozen particle composition, or frozen piercing implement and
introducing carbon dioxide gas while maintaining the mixture under
pressure. (See e.g., U.S. Pat. Nos. 4,289,794; 4,289,790;
4,262,029; 5,439,698, each of which is incorporated herein by
reference). The carbon dioxide may also be present as a clathrate
compound.
In one embodiment, at least one gasified frozen particle
composition, or frozen piercing implement is formed, for example,
by contacting fluid with gas under high pressure for a sufficient
time period to form a gas hydrate. This gas hydrate is then cooled
to a lower temperature in order to freeze the remaining unreacted
fluid and entrap the gas hydrate. As one non-limiting example,
aqueous liquid and carbon dioxide are kept in contact at
approximately 0.degree. C. for a time sufficient under a pressure
range including at least approximately 200 psig to approximately
600 psig, while permitting absorption in the liquid of the gas in
bound form and formation of the gasified ice. This process yields
approximately 25-27.5 milliliters of gas per gram of ice. (See
e.g., U.S. Pat. Nos. 4,487,023; 2,975,603; 3,086,370; 3,217,503,
and 4,404,807, each of which is incorporated herein by
reference).
Similarly, as described in U.S. Pat. No. 2,975,603, which is
incorporated herein by reference, water contacted with carbon
dioxide at a pressure of approximately 400 psig, in a temperature
bath of approximately 0.degree. C., is subsequently placed at
-10.degree. C. for 24 hours to effect degasification. As described
in U.S. Pat. No. 2,975,603, the resulting product yields
approximately 75 volumes of carbon dioxide per gram of ice.
Additionally, as described in U.S. Pat. No. 3,086,370, which is
incorporated herein by reference, gasified ice products are
produced in a similar manner that contain other gases, such as
nitrous oxide, sulfur-containing gases, chlorine-containing gases,
inert gases, or carbon monoxide.
In one embodiment, the one or more explosive materials include at
least one of sodium bicarbonate, citric acid, or both. In one
embodiment, the one or more explosive materials include hydrogen
peroxide.
In certain instances, the at least one frozen particle composition,
or frozen piercing implement is configured to explode during or
upon administration. In certain instances, the at least one frozen
particle composition, or frozen piercing implement is configured to
explode prior to or subsequent to administration. In certain
instances, the at least one frozen particle composition, or frozen
piercing implement explodes after a prolonged time subsequent to
administration or delivery to at least one biological tissue, or
other substrate. For example, in one embodiment, the one or more
explosive materials are encased or associated with a polymer or
other agent that may insulate one or more reactant or retard the
explosive or decomposition process.
Therapeutic Agents
In one embodiment, the at least one frozen particle composition, or
frozen piercing implement includes at least one therapeutic agent.
(See, e.g., The Merck Index, 14.sup.th Ed. Merck & Co., Inc.,
Whitehouse Station, NJ (2006), which is incorporated herein by
reference). Other therapeutic agents that are approved for use in
humans can be utilized as at least one therapeutic agent described
herein, and can be found at the U.S. Food and Drug Administration
website on the worldwide web, the information at which is
incorporated herein by reference.
In certain instances, the one or more frozen particles themselves
provide at least one therapeutic benefit. In certain instances, the
one or more frozen particles act as vehicles for one or more
therapeutic agents that provide at least one therapeutic benefit.
In one embodiment, the one or more frozen particles including at
least one therapeutic agent is inert.
In one embodiment, the at least one therapeutic agent includes at
least one of an anti-tumor agent, antimicrobial agent,
anti-coagulant, anti-viral agent, analgesic, antiseptic,
anesthetic, diagnostic agent, anti-inflammatory agent, vaccine,
cell growth inhibitor, cell growth promoter, chemical debridement
agent, immunogen, antigen, radioactive agent, apoptosis promoting
factor, angiogenic factor, anti-angiogenic factor, hormone,
enzymatic factor, enzyme, papain, collagenase, protease, peptidase,
elastase, urea, vitamin, mineral, nitrite, nitrate, nutraceutical,
histatin, honey, alcium alginate, angiogenic factor, hormone,
vitamin, mineral, nutraceutical, cytokine, chemokine, probiotic,
sterol, contraceptive, coagulant, anti-coagulant, phage, prodrug,
prebiotic, blood sugar stabilizer, smooth muscle cell activator,
epinephrine, adrenaline, neurotoxin, neuro-muscular toxin,
Botulinum toxin type A, microbial cell or component thereof, or
virus or component thereof. In one embodiment, the nutraceutical
includes one or more of a flavonoid, antioxidant, beta-carotene,
anthocyanin, alpha-linolenic acid, omega-3 fatty acids, yeast,
bacteria, algae, other microorganisms, plant products, or animal
products. In one embodiment, the analgesic or anesthetic includes
one or more of any aminoamid or aminoester local anesthetic,
ibuprofen, morphine, codeine, aspirin, acetaminophen,
lidocaine/lignocaine, ropivacaine, mepivacaine, benzocaine,
chloroprocaine, cocaine, cyclomethycaine, dimethocaine/larocaine,
propoxycaine, procaine/novocaine, proparacaine,
tetracaine/amethocaine, articaine, bupivacaine, carticaine,
cinchocaine/dibucaine, etidocaine, levobupivacaine, piperocaine,
prilocalne, trimecaine, saxitoxin, or tetrodotoxin.
In one embodiment, the therapeutic agent includes at least one
anti-inflammatory agent, including but not limited to steroids
(e.g., betamethasone, hydrocortisone, and derivatives thereof),
non-steroidal anti-inflammatory drugs, topical anti-inflammatory
agents, or subcutaneously administered non-steroidal
anti-inflammatory drugs (e.g. diclofenac). In one embodiment, the
therapeutic agent includes one or more of: anti-freeze substances
(e.g., polyethylene glycol), antisporiasis agents (e.g., dovonex,
tazarotene, tars, etc.), pigments (e.g., dihyroxyacetone, melanin,
hemoglobin, hemosiderin, iron copper, etc.), depigmenters (e.g.,
hydroquinone, phenolic compounds, etc.), tattoo colorants (e.g.,
skin dyes), preservatives (e.g., benzoate, paraben, or salicylate
compounds), antioxidants (e.g., conezyme Q, vitamins, etc.),
anesthetics (e.g., xylocalne, bupivicane, carbocane, amid or
ester-based anesthetics, etc.), vasoconstrictors (e.g.,
epinephrine, ephedrine, or congeners thereof, etc.), acids (e.g.,
alpha-hydroxy acid, beta-hydroxy acid, halogenated acetic acid,
etc.), irritants (e.g., acids, bases, croton oil, soap, salts of
fatty acids, etc.), antibiotics (e.g., penicillin, amoxicillin,
erythromyc in, tetracycline, monocycline, minocycline, mupirocin,
flagyl, ciprofloxacin, polymixin, gentamycin, etc.), antivirals
(e.g., acyclovir, famciclovir, valtrex, etc.), antifungals (e.g.,
imidazole, nystatin, griseofulvin, sporonox, etc.), depilatories
(e.g., eflornithine hydrochloride), proanthrocyanins (e.g.,
maritime pine extract, tocopheryl acetate, etc.), or other
substances utilized for diagnostic, prophylactic, or treatment of
afflicting conditions.
In one embodiment, the analgesic includes but is not limited to one
or more of paracetamol (acetaminophen), non-steroidal
anti-inflammatory drugs (NSAIDs), salicylates, narcotics, or
tramadol. In one embodiment, the analgesic includes but is not
limited to aspirin, rofecoxib, celecoxib, morphine, codeine,
oxycodone, hydrocodone, diamorphine, pethidine, buprenorphine,
amitriptyline, carbamazepine, bagapentin, pregabalin, ibuprofen,
naproxen, lidocaine, a psychotropic agent, orphenadrine,
cyclobenzaprine, scopolamine, atropine, gabapentin, methadone,
ketobemidone, or piritramide.
In one embodiment, the at least one therapeutic agent includes one
or more antiseptic, including but not limited to one or more of an
alcohol, a quaternary ammonium compound, boric acid, hydrogen
peroxide, chlorhexidine gluconate, iodine, mercurochrome,
octenidine dihydrochloride, phenol (carbolic acid) compounds,
sodium chloride, superoxidized water, superoxidized solution,
oxidative reductive potential solution, or sodium hypochlorite.
In one embodiment, the antiseptic includes but is not limited to
one or more of povidone-iodine, iodine, ethanol, 1-propanol,
2-propanol/isopropanol, benzalkonium chloride, cetyl
trimethylammonium bromide, cetylpyridinium chloride, benzethonium
chloride, chlorhexidine, octenidine dihydrochloride, or carbolic
acid.
In one embodiment, the at least one therapeutic agent is an
antimicrobial agent, and includes at least one of an anti-fungal
agent, antibiotic agent, anti-bacterial, anti-parasitic agent, or
anti-worm agent. In certain instances, the antimicrobial agent may
occur in nature, or it can be synthetic.
In one embodiment, the at least one therapeutic agent includes one
or more of a penicillin, cephalosporin, polymixin, sulfonamide,
beta-lactam antibiotic, beta-lactamase inhibitor, enediynes,
lincosamide antibiotic, nitroimidazole antibiotic, pleuromutilin
antibiotic, polyketide antibiotic, polymyxin antibiotic,
polypeptide antibiotic, antimicrobial peptides, quinolone
antibiotic, rifamycin antibiotic, sulfonamide antibiotic,
tetracycline antibiotic, aminoglycoside antibiotic, macrolide,
tetracycline, cyclic lipopeptide, glycylcycline, or oxazolidinone.
In one embodiment, the at least one therapeutic agent includes one
or more of amoxicillin, tobramycin, levofloxacin, gatifloxacin,
moxifloxacin, streptomycin, oxytetracycline, chloramphenicol, or
ampicillin.
In one embodiment, the at least one therapeutic agent includes one
or more anti-tumor agent, at least one of which may also be
identified as a cytotoxic agent, or chemotherapy agent.
Non-limiting examples of an anti-tumor agent for use as described
herein include at least one of an alkylating agent, antimetabolite,
anthracycline, plant alkaloid (such as paclitaxel), topoisomerase
inhibitor, monoclonal antibody, or tyrosine kinase inhibitor. In
one embodiment, the therapeutic agent includes one or more of
imatinib, mechlorethamine, cyclophosphamide, chlorambucil,
azathioprine, mercaptopurine, vinca alkaloid, taxane, vincristine,
vinblastine, vinorelbine, vindesine, podophyllotoxin, etoposide,
teniposide, amsacrine, dactinomycin, trastuzumab, cetuximab,
rituximab, bevacizumab, dexamethasone, finasteride, tamoxifen,
goserelin, telomerase inhibitor, dichloroacetate, aminopterin,
methotrexate, pemetrexed, raltitrexed, cladribine, clofarabine,
fludarabine, pentostatin, thioguanine, cytarabine, decitabine,
fluorouracil/capecitabine, floxuridine, gemcitabine, enocitabine,
sapacitabine, chloromethine, cyclophosphamide, ifosfamide,
melphalan, bendamustine, trofosfamide, uramustine, carmustine,
fotemustine, lomustine, nimustine, prednimustine, ranimustine,
semustine, spretpozocin, carboplatin, cisplatin, nedaplatin,
oxaliplatin, triplatin tetranitrate, satraplatin, busulfan,
mannosulfan, treosulfan, procarbazine, decarbazine, temozolomide,
carboquone, ThioTEPA, triaziquone, triethylenemelamine, docetaxel,
larotaxel, ortataxel, tesetaxel, vinflunine, ixabepilone,
aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin,
amrubicin, pirarubicin, valrubicin, zorubicin, metoxantrone,
pixantrone, actinomycin, bleomycin, mitomycin, plicamycin,
hydroxyurea, camptothecin, topotecan, irinotecan, rubitecan,
belotecan, altretamine, amsacrine, bexarotene, estramustine,
irofulven, trabectedin, cetuximab, panitumumab, trastuzumab,
rituximab, tositumomab, alemtuzumab, bevacizumab, edrecolomab,
gemtuzumab, axitinib, bosutinib, cediranib, dasatinib, erlotinib,
gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib,
sorafenib, sunitinib, vandetanib, alvocidib, seliciclib,
aflibercept, denileukin diftitox, aminolevulnic acid, efaproxiral,
porfimer sodium, talaporfin, temoporfin, verteporfin, alitretinoin,
tretinoin, anagrelide, arsenic trioxide, asparaginase/pegaspergase,
atrasentan, bortezomib, carmofur, celecoxib, demecolcine,
elesclomol, elasamitrucin, etoglucid, lonidamine, lucanthone,
masoprocol, mitobronitol, mitoguanzone, mitotane, oblimersen,
omacetaxine, sitimagene ceradenovec, tegafur, testolactone,
tiazofurine, tipifarnib, or vorinostat.
In one embodiment, at least one nutraceutical is included. At least
one nutraceutical includes but is not limited to, one or more of an
extract of plant or animal matter (e.g., an oil, aqueous, or solid
extract), a vitamin, a mineral, a mixture or solution, a food
supplement, a food additive, a food fortification element, or other
nutraceutical. In one embodiment, at least one nutraceutical
includes but is not limited to resveratrol, an antioxidant,
psyllium, sulforaphane, isoflavonoid, alpha-linolenic acid,
beta-carotene, anthocyanins, phytoestrogens, polyphenols,
polyphenons, catechins, benzenediols, tannins, phenylpropanoids,
caffeine, alcohol, or others.
In one embodiment, at least one therapeutic agent includes one or
more vaccine or other prophylactic therapy. In one embodiment, the
therapeutic agent includes a diagnostic agent. In one embodiment,
the frozen particle composition, or frozen piercing implement
including at least one vaccine includes at least one prophylactic
vaccine or therapeutic vaccine. In one embodiment, the at least one
therapeutic vaccine includes at least one anti-cancer vaccine. In
one embodiment, the at least one vaccine includes at least one of a
tumor antigen, microbial antigen, viral antigen, immunogen,
antigen, live microbe, dead microbe, attenuated microbe, microbe or
component thereof, live virus, recombinant virus, killed virus,
attenuated virus, virus component, plasmid DNA, nucleic acid, amino
acid, peptide, protein, glycopeptide, proteoglycan, glycoprotein,
glycolipid, sphingolipid, glycosphingolipid, cancer cell or
component thereof, organic or inorganic small molecule, or
toxoid.
One or more vaccine may include but not be limited to, vaccines
containing killed microorganisms (such as vaccines for flu,
cholera, bubonic plague, and hepatitis A), vaccines containing
live, attenuated virus or other microorganisms (such as vaccines
for yellow fever, measles, rubella, and mumps), live vaccine (such
as vaccines for tuberculosis), toxoid (such as vaccines for
tetanus, diphtheria, and crotalis atrox), subunit of inactivated or
attenuated microorganisms (such as vaccines for HBV, VLP, and HPV),
conjugate vaccines (such as vaccines for H. influenzae type B),
recombinant vector, DNA vaccination. In one embodiment, the at
least one vaccine includes but is not limited to rubella, polio,
measles, mumps, chickenpox, typhoid, shingles, hepatitis A,
hepatitis B, diphtheria, pertussis, rotavirus, influenza,
meningococcal disease, pneumonia, tetanus, rattlesnake venom,
virus-like particle, or human papillomavirus, or anti-cancer
vaccine.
In one embodiment, the at least one therapeutic agent includes at
least one adjuvant. The at least one adjuvant may include but not
be limited to one or more organic or inorganic compounds. The at
least one adjuvant may include but not be limited to at least one
of a liposome, virosome, lipid, phospholipid, mineral salt,
single-stranded stranded DNA, double-stranded RNA, aluminum salts,
microbial components carrying pathogen-associated molecular
patterns (e.g., Toll-like receptor ligands or agonists),
lipopolysaccharide, molecular antigen cage, CpG motif (e.g., CPG
oligodeoxynucleotides), microbial cell wall or component thereof,
squalene, oil emulsion, surfactant, saponin, isolated microbial
toxin, modified microbial toxin, endogenous immunomodulator, or
cytokine. In one embodiment, the at least one adjuvant and the at
least one vaccine are located in at least one of the same cavities
of the same frozen particle composition. In one embodiment, the at
least one adjuvant and the at least one vaccine are located in
different cavities of the same frozen particle composition, or
frozen piercing implement. In one embodiment, two or more frozen
particle compositions, or frozen piercing implements of a plurality
of frozen particle compositions, or frozen piercing implements
include one or more similar vaccines. In one embodiment, two or
more frozen particle compositions, or frozen piercing implements of
a plurality of frozen particle compositions, or frozen piercing
implements include one or more dissimilar vaccines.
In one non-limiting example, a composition includes one or more
frozen particle compositions, or frozen piercing implements
including paclitaxel and at least one other constituent including
at least one frozen component including air, oxygen, nitrogen,
carbon dioxide, hydrogen oxide, helium, neon, xenon, krypton,
chlorine, bromine, methane, or argon.
In one non-limiting embodiment, a composition or implement includes
one or more frozen particles including one or more pegylated
cytokines or one or more anti-tumor compounds; wherein the one or
more frozen particles include nitrogen, air, oxygen, carbon
dioxide, hydrogen oxide, helium, xenon, krypton, chlorine, bromine,
methane, or argon.
Adhesive Agents
In one embodiment, at least one adhesive agent is included in one
or more frozen particle compositions, or frozen piercing
implements. In one embodiment, the at least one adhesive agent
includes at least one monomer, prepolymer, polymer, or copolymer.
In one embodiment, the at least one adhesive agent includes at
least one monomer of self-polymerizing agent. In one embodiment,
the at least one adhesive agent is configured to polymerize upon
administration to at least one substrate. In one embodiment, the at
least one adhesive agent is configured to polymerize at or above
the temperature of the at least one substrate. In one embodiment,
the at least one adhesive agent is configured to polymerize at or
above the temperature of at least one biological tissue. In one
embodiment, the at least one adhesive agent is configured to
polymerize at or above the temperature of at least one subject.
In one embodiment, the at least one adhesive agent includes one or
more of a cement, glue, paste, fixative, or bonding agent. In one
embodiment, the at least one adhesive agent includes one or more of
a solid, liquid, or gas.
In one embodiment, the at least one adhesive agent is at least one
of non-toxic, biocompatible, biodegradable or bioresorbable. In one
embodiment, the at least one adhesive agent resists biodegradation
or bioresorption. In one embodiment, the at least one adhesive
agent is not biocompatible, or may induce a response from the at
least one biological tissue, or subject's body. In one non-limiting
example, one or more frozen particle compositions, or frozen
piercing implements are administered with or contain at least one
therapeutic agent, such as a vaccine, and optionally, at least one
adhesive agent (which may act as an adjuvant).
In one embodiment, the at least one adhesive agent is degradable or
resorbable (e.g., dissolvable sutures constructed from or secured
with an adhesive). See e.g., Sierra, and Saltz, "Surgical Adhesives
and Sealants," Technomic Pub. Co., 1996, which is incorporated
herein by reference. In one embodiment, the at least one adhesive
agent stimulates cell or tissue growth, allowing for healing of a
wound (e.g., burn, surgery incision, etc.) while the adhesive agent
itself subsequently degrades, dissolves, or is resorbed by the at
least one substrate, including at least one biological tissue or
the subject's body. In one embodiment, the at least one adhesive
agent stimulates or increases tissue regeneration. In one
embodiment, the at least one adhesive agent suppresses or decreases
scarring or keloid formation or recurrence.
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements include at least one liquid adhesive
agent. For example, the freezing point of acrylic or epoxy resins
is generally approximately -10.degree. C. to -15.degree. C., while
the freezing point of hydrogen oxide water is approximately
0.degree. C. Thus, in one embodiment, one or more frozen hydrogen
oxide particle compositions, or frozen hydrogen oxide piercing
implements include at least one liquid adhesive agent.
In one embodiment, the at least one adhesive agent includes one or
more of a hemostat, such as a mechanical hemostat (including but
not limited to, porcine gelatin, bovine gelatin, oxidized
regenerated cellulose, or polysaccharide spheres), an active
hemostat (including but not limited to, bovine thrombin, human
pooled thrombin, or recombinant thrombin), a flowable hemostat
(including but not limited to, bovine gelatin and human thrombin,
or porcine gelatin with or without thrombin), or a hemostat and
sealant (such as fibrin sealants of human pooled fibrin; human
fibrin; plasma, collagen, and bovine thrombin; animal fibrin or
thrombin, or others). In one embodiment, the adhesive agent
includes one or more of a sealant (such as polyethylene glycol
(PEG) polymers, including dual PEG or single PEG). In one
embodiment, the adhesive agent includes but is not limited to
albumin (such as bovine serum albumin) and glutaraldehyde. (See,
for example, Spotnitz and Burks, Transfusion, pp. 1502-1516, Vol.
48, 2008; which is incorporated herein by reference.) In one
embodiment, the adhesive agent is part of one or more adhesive
laminates which include at least one adhesive agent and at least
one non-adherent substance (which may optionally be biocompatible,
bioresorbable, biodegradable, or nontoxic). See, for example, U.S.
Patent Application Publication No. 20050153090, which is
incorporated herein by reference.
In one embodiment, the at least one adhesive agent includes at
least one naturally-occurring substance, such as gelatin, blood
plasma, albumin, collagen, fibrin, fibrinogen (including lytic
fragments, for example FPA, FPB, fragments D and E), hyaluronate,
hyaluronan, glycosaminoglycans, chitin, thrombin, Factor XIII, or
other substances. In one embodiment, the at least one adhesive
agent includes at least one artificial or synthetic substance, such
as an acrylic polymer or copolymer, acrylamide polymer or
copolymer, polyacrylic acid (including but not limited to zinc
polycarboxylate, resin bonding, or glass ionomer cement), epoxy,
urethane, gum arabic, polyester, polyhydroxyalkanoate,
poly(L-lactic acid), polyglycolide, polylactic acid, polyether,
polyol, polyvinylpyrrolidone, pyroxylin,
polymethyacrylate-isobutene-monoisopropylmaleate, siloxane polymer,
polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly(e-caprolactone), sialyl
Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, polyelectrolyte, maleic polyelectrolyte, cellulose,
resilin, cyanoacrylate, isocyanate, (including but not limited to
2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate, monomeric
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, or its higher homologs (ethyl, butyl, octyl,
etc.), or polyisohexylcyanoacrylate), fibrin, thrombin,
firbrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, albumin, glutaraldehyde, polyethylene glycol,
hydrogel, soy or other plant based adhesives, or gelatin. In at
least one embodiment, the adhesive agent includes gecko glue. In at
least one embodiment, the adhesive agent includes microscopic seta
configured to adhere by van der Waals forces.
In one embodiment, the at least one adhesive agent includes one or
more of a globin, hemoglobin, heme group, carbohydrate, cell or
cell component, silicone, hydroxyapatite, acrylic polymer or
copolymer, acrylamide polymer or copolymer, hyaluronate or
hyaluronic acid, carboxymethylcellulose, healon, polymer or
biopolymer, gelatin-resorcinol-formaldehyde (GRF) combination, a
fibrin-collagen combination, or a fibrinogen-thrombin combination.
In one embodiment, the at least one adhesive agent includes one or
more naturally-occurring, artificial, or synthetic polymers,
including but not limited to urethane prepolymers or polymers,
cyano-based polymers, polyether, polyol, polyvinylpyrrolidone,
pyroxylin/nitrocellulose,
polymethylacrylate-isobutene-monoisopropylmaleate, acrylate
polymers or siloxane polymers (such as acrylate terpolymer,
polyphenylmethylsiloxane, hexamethyldisiloxane or isooctane solvent
based polymers). (For other specific examples of adhesive agents
see, e.g., U.S. Pat. Nos. 4,740,534 and 7,264,823; and U.S. Patent
Application Nos. 20040097990, 20070161109, and 20070031474, each of
which is incorporated herein by reference). In one embodiment, the
at least one adhesive agent includes a combination of more than one
adhesive agents.
In one embodiment, the at least one adhesive agent includes at
least one crosslinking or derivatized agent. In one embodiment, the
at least one adhesive agent is configured to form a crosslink bond
with at least one component of at least one substrate. In one
embodiment the crosslink bond of the at least one adhesive agent is
configured for modulation by one or more of a chemical agent,
change in pH, change in exposure to air, vacuum, change in moisture
content, change in pressure, or change in temperature. In one
embodiment, the formation of a crosslink bond of the at least one
adhesive agent is configured for modulation by exposure of the at
least one adhesive agent to one or more of electromagnetic energy,
optical energy, thermal energy, laser energy, ionizing radiation,
non-ionizing radiation, or sonic energy.
In one embodiment, one or more constituent of the at least one
adhesive agent includes a crosslinked constituent (such as gelatin
or albumin that is cross-linked with, for example, glutaraldehyde),
or a derivatized constituent (such as derivatized collagen). In one
embodiment, the at least one adhesive agent includes one or more
constituents that are configured to crosslink with one or more
substances in the at least one biological tissue. The crosslinking
bond can form upon administration of the at least one adhesive
agent to the at least one biological tissue, or upon administration
of at least one of a chemical agent (such as an acid, base, enzyme,
epoxide, diepoxide, 1,4-butanediol diglycidyl ether,
glutaraldehyde, polysaccharide, or other chemical agent), air,
moisture (such as from a biological fluid), electromagnetic energy
(including ultraviolet light), optical energy, thermal energy,
laser energy, ionizing radiation, non-ionizing radiation, or sonic
energy to the at least one adhesive agent.
In one embodiment, the at least one adhesive agent includes one or
more protein glue, including but not limited to protein, peptide,
or amino acid-based substances. In one embodiment, the at least one
adhesive agent includes one or more naturally-occurring or
synthetic component. In one embodiment, the at least one adhesive
agent includes one or more naturally-occurring or synthetic
polyphenolic protein from mussels, wherein the polyphenolic protein
is optionally cross-linked by a catechol oxidase. In one
embodiment, the at least one adhesive agent includes mussel
adhesive protein. In one embodiment, the mussel adhesive protein
includes lysine, hydroxylated amino acids, and dopa. In certain
instances, the mussel adhesive protein includes
dihydroxyphenylalanine. In one embodiment, the at least one
adhesive agent includes prolamine. In one embodiment, the at least
one adhesive agent includes one or more chemotactic agent, such as
transforming growth factor beta (TGF-.beta.).
In one embodiment, fibrin sealant or fibrin glue can be formed as
indicated in the table herein, or from two components: one
containing fibrinogen and calcium chloride solution and the other
containing thrombin solution and epsilon amino caproic acid
(EACA).
In one embodiment, the at least one adhesive agent includes one or
more hydrogel. See, for example, U.S. Pat. No. 6,103,528, which is
incorporated herein by reference. One non-limiting example of a
hydrogel included in a composition as described herein includes
polyethylene glycol, polylactic acid, polytrimethylene carbonate,
polycarophil, carbopol, polyox, chitosan, polyvinylpyrrolidone,
block polymers or block copolymers, polymethylvinyl ether-maleic
anhydride, or other constituents. In certain embodiments, the
hydrogel may include a constituent with a polymerizable end cap,
such as an acrylate ester. In one embodiment, the at least one
adhesive agent at least partially generates a wound dressing, such
as a sheet, bandage, film, or other permeable, semi-permeable, or
impermeable covering. In one embodiment, the at least one wound
dressing at least partially includes natural, synthetic, or
artificial skin or skin deposit. (See, for example, Boateng et al.,
J. Pharm. Sciences. vol. 97, pp. 2892-2923 (2008)).
Some specific non-limiting examples of particular adhesive agents
that are included in at least one composition described herein are
listed in Table II herein. (Adapted from Smith, Ch. 7, p. 574,
Table 1; Ratner, et al, Biomaterials Science, Second Edition, 2004;
Elsevier Acad. Press., which is incorporated herein by
reference).
TABLE-US-00003 TABLE II Type of Possible setting or tissue
Components bonding reaction Cyanoacrylate Butyl or isobutyl
Addition polymerization cyanoacrylate Fibrin Fibrinogen (with or
without Clot formation sealant Factor XIII) Thrombin, CaCl.sub.2
Factor XIII Clot formation GRF glue Gelatin, resorcinol,
Condensation formaldehyde (glutaraldehyde or glyoxal can be used in
addition to or instead of formaldehyde) Hydrogel Block copolymers
of PEG, Photoinitiated addition polylactic acid and acrylate
polymerization esters Acrylic bone Methyl methacrylate and
Pertoxide-amine initiated cement polymethyl methacrylate addition
polymerization Dental Zinc oxide powder, Acid-base reaction, zinc
cements phosphoric acid complexation Zinc Zinc complexation
phosphate Zinc poly- Zinc oxide powder, aqueous Acid-base reaction,
zinc carboxylate polyacrylic acid complexation Glass Ca, Sr, Al
silicate glass Acid-base reaction, metal ionomer powder aqueous
poly- ion complexation (poly- acrylic-itatomic acid or alkenoate)
polyacrylic-maleic acid Resin-based Aromatic or urethane
Peroxide-amine or dimethacrylate monomers, photoinitiated silicate
or other glass polymerization and fillers aqueous polyacrylic
photoinitiated addition acid-itaconic acid-meth- polymerization
acrylate comonomers Resin- Hydroxyethyl methacrylate modified
aromatic or urethane glass diamethacrylates, Ca, Sr, Al ionomer
glass powder Dentin Etchant: phosphoric acid Photoinitiated
addition adhesive primer: carboxylate or polymerization phosphate
Monomers hydroxyethyl methacrylate/water/solvent Bonding agent:
urethane or aromatic dimethacrylate monomers
In one embodiment, the at least one adhesive agent is configured to
convert to at least one therapeutic agent upon administration of
the at least one adhesive agent. In one embodiment, the at least
one adhesive agent is configured to undergo one or more of
hydration, hydrolysis, hydrogenolysis, condensation, dehydration,
or polymerization upon administration of the at least one adhesive
agent. In one embodiment, the at least one adhesive agent includes
a methacrylate. In one embodiment, the at least one adhesive agent
includes at least one of
poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2'-(methacryloyloxy)ethyl]--
ammonium bromide) or poly(sulfobetaine methacrylate).
In one embodiment, the at least one adhesive agent is configured to
form one or more of a hydrogen bond, ionic bond, covalent bond, or
noncovalent bond with at least one substrate.
In certain instances, at least one adhesive agent is provided to at
least one substrate, including but not limited to at least one
biological tissue, in an inactive form. In certain instances, the
at least one adhesive agent is configured to polymerize or activate
during administration of the at least one adhesive agent to at
least one substrate, or shortly thereafter.
In one embodiment, the at least one adhesive agent is compatible
with moist or wet tissues. In one embodiment, the at least one
adhesive agent distributes evenly over the tissue surface. In one
embodiment, the at least one adhesive agent quickly forms a durable
bond. In one embodiment, the bonding time of the at least one
adhesive agent is controllable. In one embodiment, the bonding time
of the at least one adhesive agent is controlled or regulated. In
one embodiment, the at least one adhesive degrades in a relatively
short period of time. In one embodiment, the at least one adhesive
agent is configured to be resorbed by the tissue to which it is
applied, or by the subject's body. In one embodiment, the at least
one adhesive agent maintains an appropriate viscosity for the
application, provides adequate working time prior to bonding or
setting, develops good adhesion, modulates hemostasis, modulates
wound healing, reduces fibrosis, or provides at least one
antimicrobial effect. In one embodiment, the at least one
composition including at least one adhesive provides a local depot
for at least one therapeutic agent.
In one embodiment, the at least one adhesive agent includes an
active surface (i.e. having a bioglass, calcium phosphate, or
biochemically active surface that can stimulate an in vivo
response). In one embodiment, the at least one adhesive agent
assists in delivering one or more therapeutic agents, including but
not limited to antibiotics, vaccines, growth factors (e.g., members
of the Fibroblast Growth Factor, members of the Bone Morphogenic
Protein family, members of the Transforming Growth Factor-beta
family, or others), transcription factors, anti-inflammatory
agents, pain relievers, hemostatic agents, chemotherapeutic agents
(e.g., 5-fluorouracil, paclitaxel, or others), chemokines,
cytokines, angiogenic or anti-angiogenic factors, enzymes, stem
cells, cellular organelles, or other therapeutic agents described
herein.
In one embodiment, the at least one adhesive agent is delivered as
a precursor molecule that is configured to activate by an
additional activation step or event. In one embodiment, two or more
components are configured to combine upon administration of the at
least one adhesive agent. In one embodiment, the combination of the
two or more components modifies at least one property of the
adhesive agent. In one embodiment, the at least one property
includes one or more of initiation of adhesive bond formation,
strength of adhesive bond, adhesive bonding time, bond flexibility,
bond biodegradability, bond bioresorbability, bond
biocompatibility, or durability of adhesive bond. In one
embodiment, the at least one property includes one or more of
polymerization of the adhesive agent, or crosslinking of the
adhesive agent. In one embodiment, two or more frozen particle
compositions, or frozen piercing implements are administered;
wherein at least one administration parameter is different for the
two or more frozen particle compositions, or frozen piercing
implements. In one embodiment, the at least one administration
parameter includes at least one of: constitution of the frozen
particle composition, or frozen piercing implement, formulation of
the frozen particle composition, or frozen piercing implement, size
of the frozen particle compositions, or frozen piercing implements,
shape of the frozen particle composition, or frozen piercing
implement, angle of administration of the frozen particle
composition, or frozen piercing implement, velocity of
administration of the frozen particle composition, or frozen
piercing implement, quantity of frozen particle compositions, or
frozen piercing implements administered, rate of administration of
more than one frozen particle composition, or frozen piercing
implement, spatial location for administration of the frozen
particle compositions, or frozen piercing implements, temporal
location for administration of the frozen particle compositions, or
frozen piercing implements, method of administration of the frozen
particle compositions, or frozen piercing implements, timing of
administration of the frozen particle compositions, or frozen
piercing implements, modulation of administration of the frozen
particle compositions, or frozen piercing implements, deposition of
the frozen particle compositions, or frozen piercing implements, or
rate of deposition of at least one agent included in the frozen
particle compositions, or frozen piercing implements.
In one embodiment, the at least one adhesive agent maintains the
approximation of tissue of at least one wound of a subject. In one
embodiment, the at least one adhesive agent forms a bond that
resists separation between at least two aspects of a substrate. In
one embodiment, the at least one adhesive agent is administered to
the at least one substrate, such as a biological tissue or
structure, prior to, during, or subsequent to a surgical procedure.
Specific, non-limiting examples of surgical procedures include
thoracic surgery, cardiovascular surgery, vascular surgery,
neurological surgery, plastic surgery or aesthetic surgery,
ophthalmic surgery, skin or connective tissue surgery, or abdominal
surgery.
In one embodiment, at least one frozen particle composition, or
frozen piercing implement includes an adhesive agent which provides
a means for the repair, closure, maintenance of approximately the
same tissue of a wound, treatment of a wound, or joining at least
one substrate to another or joining at least one aspect of a
substrate to another aspect of the same or different substrate.
In one embodiment, and as described herein, compositions and
methods relate to the same or different frozen particle
compositions, or frozen piercing implements, and are administered
simultaneously, sequentially, randomly, or in another order. In
certain instances, the at least one composition is administered
that contains at least one adhesive agent as well as one or more
other agents, such as bonding agents, that include functional
groups or reactive side chains.
In one non-limiting example, polymerizable dimethacrylate monomers
mixed with composite formulations are administered to calcified
tissue, such as bone or tooth. In another non-limiting example,
acid etching or priming of the cell or tissue surface (such as a
calcified surface), is achieved by administration of phosphoric
acid or another acidic substance. In certain instances, the acidic
substance includes functional groups, such as polycarboxylate or
polyphosphate. Next, one or more agents can be administered that
react with the functional groups, such as hydrophilic monomers
(including but not limited to hydroxyethyl methacrylate).
In one embodiment, the at least one adhesive agent forms one or
more of a hydrogen bond, ionic bond, covalent bond, or non-covalent
bond upon administration to at least one substrate. In one
embodiment the at least one adhesive agent includes at least one
crosslinking or derivatized agent. In one embodiment, the at least
one adhesive agent forms a crosslink bond with at least one
component of at least one substrate to which the adhesive agent is
administered. In one embodiment, the crosslink bond of the at least
one adhesive agent is modulated by one or more of a chemical agent,
change in pH, change in exposure to air, vacuum, change in moisture
content, change in pressure, or change in temperature. In one
embodiment, formation of a crosslink bond of the at least one
adhesive agent is modulated by exposure of the at least one
adhesive agent to one or more of electromagnetic energy, optical
energy, thermal energy, laser energy, ionizing radiation,
non-ionizing radiation, or sonic energy.
In one embodiment, adhesive agents can be selected for a particular
use as described herein, based on factors including, but not
limited to, viscosity, adhesive tenacity, kinetic rates of monomer
formation, polymerization (with or without covalent cross-linking),
ability to be cryoprecipitated, tensile strength, ability to
restore biomechanical tissue integrity, in vivo effectiveness, or
other factors. In certain instances, these or other factors can be
measured and selection of the one or more particular adhesive
agents can be based on those measurements. In certain instances,
these or other factors can be measured by standard methods,
including but not limited to, in vitro analysis, in vivo
experiments (e.g., animal studies), ex vivo experiments, in planta
experiments, or other methods.
In one embodiment, a method for providing at least one agent to at
least one substrate comprises administering at least one frozen
particle composition, or frozen piercing implement to at least one
substrate, wherein the at least one frozen particle composition, or
frozen piercing implement includes one or more frozen particles as
described herein, and at least one agent.
In one embodiment, a method for providing at least one adhesive
agent to at least one substrate comprises administering at least
one frozen particle composition, or frozen piercing implement to at
least one substrate, wherein the at least one frozen particle
composition, or frozen piercing implement includes one or more
frozen particles as described herein, and at least one adhesive
agent.
In one embodiment, a method of maintaining the approximation of
tissue of at least one wound of a subject comprises administering
at least one frozen particle composition, or frozen piercing
implement to at least one wound of a subject for a time sufficient
to maintain the approximation of tissue of the at least one wound;
wherein the at least one frozen particle composition, or frozen
piercing implement includes one or more frozen particle
compositions, or frozen piercing implements including at least one
agent (such as an adhesive agent, biological remodeling agent,
reinforcement agent, therapeutic agent, abrasive, or explosive
material) as described herein.
In one embodiment, the at least one frozen particle composition, or
frozen piercing implement includes a detection state that varies
with its adhesive state. In one embodiment, the adhesive agent
includes one or more eposy adhesive, acrylic adhesive, urethane
adhesive, polyurethane adhesive, silicone adhesive, cationic
adhesive, anerobic adhesive, urethane acrylate, polyester acrylate,
methacrylate, methyacrylate, or cyanoacrylate.
In one embodiment, the at least one adhesive agent includes at
least one .alpha.-cyanoacrylate and a fluorescent compound
including at least one of a bis-benzoxazolyl compound, pyrylium
salt, quantum dot, or coumarin compound. In one embodiment, the at
least one adhesive agent includes an .alpha.-cyanoacrylate and
2,5-bis-(5-tert-butyl-2-benzoxasolyl)-thiophene. In one embodiment,
the at least one adhesive agent includes one or more of a base
component, initiator component, or activator component. In one
embodiment, the at least one adhesive agent further includes at
least one curing component. In one embodiment, the at least one
adhesive agent includes at least one photopolymerizable adhesive,
photocurable adhesive, thermal curable adhesive, free radical
curable adhesive, or aerobic curable adhesive. In one embodiment,
the at least one adhesive agent includes one or more adhesive agent
configured to polymerize upon exposure to infrared light,
ultraviolet light, x-ray, visible light, or other electromagnetic
radiation.
In one embodiment, the adhesive agent includes at least one dye
coinitiator. In one embodiment, the at least one dye coinitiator
includes at least one of a bis-benzoxazolyl compound, pyrylium
salt, QTX, safranine O, fluorescein, eosin yellow, eosin Y, eosin
B, ethyl eosin, eosin bluish, erythrosine B, erythrosine yellowish
blend, toluidine blue, 4',5'-dibromofluorescein, Rose Bengal B,
cyanine, pyronin GY, cresyl violet, brilliant green, lissamine
green BN, rhodamine B, methylene blue, crystal violet, phosphine
oxide, or coumarin compound.
Biological Remodeling Agents
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements include at least one biological
remodeling agent. In one embodiment, the at least one biological
remodeling agent includes one or more extracellular matrix
components. In one embodiment, the at least one biological
remodeling agent is configured to provide at least one chemical or
biochemical function to the at least one biological tissue. In one
embodiment, the biological remodeling agent is configured to
modulate the growth of at least one biological tissue. In one
embodiment, the biological remodeling agent is configured to
promote growth of at least one biological tissue. In one
embodiment, the at least one biological remodeling agent is
configured to promote at least one of cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, angiogenesis, diffusion of materials,
nucleic acid expression, protein translation, protein modification,
protein secretion, carbohydrate production, carbohydrate secretion,
fat production, or fat secretion.
In one embodiment, the biological remodeling agent is configured to
inhibit growth of at least one biological tissue. In one
embodiment, the at least one biological remodeling agent is
configured to inhibit at least one of cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, angiogenesis, diffusion of materials,
nucleic acid expression, protein translation, protein modification,
protein secretion, carbohydrate production, carbohydrate secretion,
fat production, or fat secretion.
In one embodiment, the at least one biological remodeling agent is
configured to promote at least partial construction or at least
partial reconstruction of at least one biological tissue. In one
embodiment, the at least one biological remodeling agent includes
at least one cellular or tissue scaffolding component (e.g.,
collagen, elastin, protein, carbohydrate, nucleic acid, organic or
inorganic agent, or other component). In one embodiment, the at
least one biological remodeling agent includes at least one cell
(e.g., endogenous cell, exogenous cell, transgenic cell, progenitor
cell, allogeneic cell, neonatal cell, embryonic cell, stem cell,
differentiated cell, blood cell, chondrocyte, endothelial cell,
hepatocyte, keratinocyte, myocyte, osteoblast, osteoclast,
osteocyte, mesenchymal cell, fibroblast, etc.), other cells are
described herein. (See, for example, Nolte et al., Cells Tissues
Organs vol. 187, pp. 165-176 (2008), which is incorporated herein
by reference.)
In one embodiment, the at least one biological remodeling agent
provides a scaffold or matrix for growth, regrowth, restructuring,
remodeling, or physically, chemically, or biologically structuring
one or more cells or biological tissues. In one embodiment, the at
least one biological remodeling agent is configured to provide at
least one mechanical structure to the at least one biological
tissue. In one embodiment, the at least one biological remodeling
agent provides a load-bearing structure to at least one biological
tissue.
In one embodiment, the at least one biological remodeling agent is
configured to provide oxygenation, nutrition, or other nourishment
to at least one biological tissue.
In one embodiment, the at least one biological remodeling agent
includes one or more self-organizing structures, including at least
one hydrogel, nanofiber, nanoparticle, or helical structure. (See,
for example, Pokroy et al, Science vol. 323, pp. 237-240 (2009);
U.S. Patent Application Publication No. 20080070304, each of which
is incorporated herein by reference.) In one embodiment, the at
least one biological remodeling agent includes one or more
self-assembling nanofibers or nanoparticles.
In one embodiment, the at least one biological remodeling agent at
least partially generates a wound dressing, such as a sheet,
bandage, film, or other permeable, semi-permeable, or impermeable
covering. In one embodiment, the at least one wound dressing at
least partially includes natural, synthetic, or artificial skin,
skin substitute, or skin deposit. In one embodiment, the at least
one biological remodeling agent includes at least one nanotube
(such as a carbon nanotube, DNA nanotube, or other nanotube).
In one embodiment, the at least one biological remodeling agent
includes at least one of a tumor antigen, microbial antigen, viral
antigen, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, chemical debridement agent, immunogen, antigen,
radioactive agent, apoptosis promoting factor, angiogenic factor,
anti-angiogenic factor, hormone, enzymatic factor, enzyme, papain,
collagenase, protease, peptidase, elastase, urea, vitamin, mineral,
nutraceutical, cytokine, chemokine, probiotic, coagulant,
anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer,
smooth muscle cell activator, epinephrine, adrenaline, neurotoxin,
neuro-muscular toxin, Botulinum toxin type A, microbial cell or
component thereof, or virus or component thereof. In one
embodiment, the nutraceutical includes one or more of a flavonoid,
antioxidant, beta-carotene, anthocyanin, alpha-linolenic acid,
omega-3 fatty acids, yeast, bacteria, algae, other microorganisms,
plant products, or animal products.
In one embodiment, a frozen particle composition, or frozen
piercing implement, comprises: one or more frozen hydrogen oxide
particles that include at least one non-nucleic acid biological
remodeling agent.
In one embodiment, the at least one biological remodeling agent is
utilized in at least partially constructing or reconstructing at
least a portion of one or more biological tissues or organs. In on
embodiment, the at least one biological remodeling agent assists in
the repair, enhancement, or replacement of at least a portion of at
least one biological tissue structure or function. In one
embodiment, the at least one biological remodeling agent assists in
restoring, maintaining, or improving at least one tissue or organ
function.
In one embodiment, at least one frozen particle composition, or
frozen piercing implement including at least one biological
remodeling agent or adhesive agent is utilized in at least
partially generating at least one biological tissue de novo. In one
embodiment, at least one frozen particle composition, or frozen
piercing implement including at least one biological remodeling
agent or adhesive agent is utilized in at least partially repairing
at least one damaged or diseased biological tissue. In one
embodiment, the at least one damaged or diseased biological tissue
is located in vivo. In one embodiment, the at least one damaged or
diseased biological tissue includes one or more wounds.
In one embodiment, a method includes at least partially
constructing or reconstructing at least one biological tissue or
organ by administering one or more frozen particle compositions, or
frozen piercing implements in such a manner that at least one agent
is deposited, wherein the one or more frozen particle compositions,
or frozen piercing implements include at least one biological
remodeling agent, at least one adhesive agent, at least one
therapeutic agent, at least one reinforcement agent, at least one
abrasive, at least one microneedle, or at least one explosive
material. In one embodiment, one or more frozen particle
compositions, or frozen piercing implements are deposited,
resulting in at least partially constructing or reconstructing at
least one biological tissue or organ.
In one embodiment, the at least one biological remodeling agent is
administered to at least one substrate, as described herein. In one
embodiment, the at least one biological remodeling agent includes
at least one nontoxic agent. In one embodiment, the at least one
biological remodeling agent includes a biocompatible,
bioresorbable, or biodegradable agent. In one embodiment, the at
least one substrate to which the one or more frozen particle
compositions, or frozen piercing implements are deposited or
administered is at least one of biocompatible, bioresorbable, or
biodegradable.
In one embodiment, at least one scaffold is utilized for
construction, reconstruction, or remodeling of at least one
biological tissue. In one embodiment, the at least one scaffold is
at least partially generated by deposition or administration of one
or more frozen particle compositions, or frozen piercing implements
including at least one biological remodeling agent. In one
embodiment, the at least one scaffold is at least one of
biocompatible, bioresorbable, or biodegradable.
In one embodiment, a template or molding is utilized for deposition
of one or more frozen particle compositions, or frozen piercing
implements including at least one biological remodeling agent. In
one embodiment, the frozen particle composition, or frozen piercing
implement includes one or more of a biological remodeling agent, a
therapeutic agent, abrasive, explosive material, adhesive agent, or
other agent. In one embodiment, the template or molding is at least
one of nontoxic, biocompatible, bioresorbable, or biodegradable. In
one embodiment, the one or more biological remodeling agents, are
deposited or administered directly onto at least one substrate that
is utilized in constructing, reconstructing, or remodeling at least
one biological tissue.
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements, including at least one biological
remodeling agent, are delivered to at least one scaffold, including
a three dimensional porous scaffold. In one embodiment, the
scaffold includes means for cell attachment, means for cell
proliferation, means for cell differentiation, means for cell
migration, means for cell contracting, means for cell expression,
means for cell matrix production, or means for cell spreading. In
one embodiment, the at least one scaffold includes seeding at least
one cell (e.g., a live cell) within at least one scaffold. In one
embodiment, seeding at least one cell within the at least one
scaffold occurs prior to, simultaneously with, or subsequent to, at
least partially generating, implanting, or transplanting the at
least one scaffold. In one embodiment, the at least one scaffold
includes injecting at least one biological remodeling agent and at
least one cell (e.g., a live cell) mixture to the at least one
substrate for at least partially constructing, reconstructing, or
remodeling at least one biological tissue. In one embodiment, the
scaffold is at least partially generated, implanted, or
transplanted and is eventually seeded with a subject's own cells,
either naturally or artificially.
In one embodiment, the at least one biological remodeling agent
includes one or more of calcium phosphate, albumin, cytokine,
pegylated cytokine, bone, cartilage, globulin, fibrin, thrombin,
glutaraldehyde-crosslinked pericardium, hide powder, hyaluronic
acid, hydroxyapatite, keratin, ligament, nitinol, nucleic acid
polymers, polyethylene, polylethylene glycol, polyethylene glycol
diacrylate, polyethylene terephthalate fiber, polyglycol,
polylactate, polytetrafluoroethylene, polylactic acid, polyglycolic
acid, polycaprolactone, PURAMATRIX.TM. self-assembly peptide
hydrogel fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, elastin, silicone,
polyurethane, ceramic powder, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or
gelatin.
In one embodiment, the at least one biological remodeling agent
includes one or more of Type I collagen, Type II collagen, Type III
collagen, Type VII collagen, or Type X collagen. In one embodiment,
the at least one biological remodeling agent includes one or more
of elastin fibers or soluble elastin.
In one embodiment, the biological remodeling agent includes at
least one member of the Transforming Growth Factor .beta.
superfamily, including but not limited to bone
morphogenetic/osteogenic proteins (BMPs/OPs), growth
differentiation factors, activin A and B, inhibin A and B,
Anti-mullerian hormone, Nodal, TGF-.beta. type receptors such as
Activin Type I receptors, Activin Type II receptors,
transducers/SMAD molecules, ligand inhibitors (e.g., Cerberus,
chordin, Dan, Decorin, Follistatin, Gremlin, Lefty, LTBP1, Noggin,
THBS1), co-receptors (e.g., BAMBI-Cripto), SARA, or other
molecules. (See, for example, Aarabi et al., PLOS Med., vol. 4,
Issue 9, pp. 1464-1470 (2007). In one embodiment, the at least one
biological remodeling agent includes one or more of epidermal
growth factor (EGF), platelet derived growth factor (PDGF),
fibroblast growth factor (FGF), insulin-like growth factor (IGF-1),
human growth hormone, granulocyte-colony stimulating factor
(G-CSF), or granulocyte-macrophage colony-stimulating factor
(GM-CSF). In one embodiment, one or more biological remodeling
agents include at least one nucleic acid. In one embodiment, one or
more biological remodeling agents include at least one RNA or DNA
molecule. In one embodiment, the one or more biological remodeling
agents include at least one of a protein, carbohydrate, or fat.
Some other non-limiting examples of biological remodeling agents,
as well as the general but non-limiting solidification mechanism of
each, are set forth in Table III below. Abbreviations include: OPF:
oligo(poly(ethylene glycol) fumarate); P(CL/TMC):
poly(-caprolactone-co-trimethylene carbonate); PDLLA:
poly(D,L-lactide); PEG: poly(ethylene glycol); PEO: poly(ethylene
oxide); PEO-PPO-PEO: polyethylene oxide-polypropylene
oxide-polyethylene oxide; PhosPEG-dMA: poly(ethylene glycol)
di[ethylphosphatidyl(ethylene glycol)methacrylate]; PLA(Glc-Ser):
Poly(L-lactic acid-co-glycolic acid-co-L-serine); PLA-PEG:
poly(lactic acid)-poly(ethylene glycol; PLAL-ASP: Poly(lactic
acid-co-lysine)-poly(aspartic acid); PLGA:
Poly(DL-lactic-co-glycolic acid); PLLA: poly(L-lactic acid);
PLLA-PEG: poly(L-lactide-ethylene glycol); PNIPAAm:
poly(N-isopropylacrylamide); P(NIPAAm-AAc):
Poly(N-isopropylacrylamide-acrylic acid); PPF: poly(propylene
fumarate); P(PF-co-EG): poly(propylene furmarate-co-ethylene
glycol; PVA: poly(vinyl alcohol). (See, for example, Hou et al., M.
Mater. Chem., vol. 14, pp. 1915-1923 (2004), which is incorporated
herein by reference.)
TABLE-US-00004 TABLE III Biological Remodeling Agent Solidification
mechanism Calcium phosphate Ceramics setting Chitosan Thermal
gelation Methylcellulose Thermal gelation Alginate Photo
cross-linking or ionic gelation Hyaluronic acid Photo cross-linking
Agarose Thermal gelation Fibrin Thermal gelation Gelatin Thermal
gelation Poly(aldehyde gluronate) Chemical cross-linking PEG or PEO
Photo cross-linking PEO-PPO-PEO Thermal gelation PEO-PLLA-PEO Photo
cross-linking PLA-g-PVA Photo cross-linking PEO-PLLA Thermal
gelation PLGA-PEG Thermal gelation PEG-co-Poly(.alpha.-hydroxy
acid) Photo cross-linking PVA, PLAL-ASP, P(CL/TMC), PLA(Glc- Photo
cross-linking Ser), or Polyanhydrides PPF, OPF, or P(PF-co-EG)
Photo cross-linking or radical polymerization PhosPEG-dMA Photo
polymerization PNIPAAm-PEG, PNIPAAm-gelatin, Thermal gelation
P(NIPAAm-AAc) PEG based hydrogels Enzymatic cross-linking or
Michael-type addition reaction PLA-PEG-biotin Self-assembly
In one embodiment, at least one frozen particle composition, or
frozen piercing implement is administered to at least one substrate
by pushing, pulling, drilling, utilizing a screw-type action,
propelling, ejecting, or accelerating a plurality of frozen
particle compositions, or frozen piercing implements toward the at
least one substrate. In one embodiment, propelling, ejecting, or
accelerating the plurality of frozen particle compositions, or
frozen piercing implements toward the at least one substrate
includes at a predetermined angle, a predetermined velocity, a
predetermined rate of administration, a predetermined spatial
pattern, a predetermined location, a predetermined time sequence,
or a predetermined depth. In one embodiment, two or more of the
plurality of frozen particle compositions, or frozen piercing
implements include two or more biological remodeling agents
configured to physically or chemically bind upon administration. In
one embodiment, administering the one or more frozen particle
compositions, or frozen piercing implements to at least one
substrate includes contacting the at least one substrate with the
one or more frozen particle compositions, or frozen piercing
implements. In one embodiment, administering the one or more frozen
particle compositions, or frozen piercing implements to at least
one substrate includes contacting the at least one substrate with
the at least one biological remodeling agent.
Substrates
In one embodiment, the one or more frozen particle compositions,
frozen piercing implements, or frozen piercing implement devices
are administered to at least one substrate. Specific non-limiting
examples of various different substrates are provided throughtout
the application.
In one embodiment, the at least one substrate includes at least one
nontoxic, biodegradable, bioresorbable, or biocompatible substrate.
In one embodiment, the at least one substrate includes one or more
of a cell, tissue, organ, structure, device, or food product. In
one embodiment, the substrate includes at least a portion of which
is naturally, artificially, or synthetically derived. In one
embodiment, the substrate includes at least a portion of which is
genetically altered. In one embodiment, at least one frozen
particle composition, or frozen piercing implement is administered
to at least one cell or cell component for gene delivery.
In one embodiment, the structure or device may include a
prosthesis, cell matrix or scaffold, tissue matrix or scaffold,
supplement, implement, bandage, tourniquet, wound dressing, splint,
stent, patch, gauze, covering, shunt, needle, scalpel, matrix,
sponge, mesh, woven fabric, knitted fabric, film, instrument, or
other tool or item. (See, for example, U.S. Patent Application
Publication No. 20070021816, which is incorporated herein by
reference.) In one embodiment, the device includes at least one
mechanical or electrical device. In one embodiment, the device
includes, but is not limited to, at least one mechanical or
electrical device. Examples of particular devices are described
herein.
In one embodiment, the substrate is located in at least one of in
situ, in vitro, in vivo, in utero, in planta, in silico, or ex
vivo. In one embodiment, the at least one substrate is transplanted
or implanted into at least one subject. In one embodiment, the at
least one substrate is ingested by at least one subject. In one
embodiment, the at least one substrate includes at least one
biological cell or tissue. In one embodiment, the at least one
biological cell or tissue is from at least one donor or recipient.
In one embodiment, the at least one donor includes at least one
cadaver. In one embodiment, the at least one substrate includes at
least one implantable or transplantable substrate. In one
embodiment, the at least one substrate is transplanted or implanted
into at least one subject. In one embodiment, the at least one
substrate includes at least one biological tissue from at least one
donor or recipient.
In one embodiment, the temperature of the substrate is adjusted for
administration of one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the temperature of
the substrate is increased or decreased in order to adjust the rate
of melting, sublimation, evaporation, transformation, activation,
etc. of the one or more frozen particle compositions, or frozen
piercing implements or a component thereof.
In one embodiment, the pressure exerted on a substrate is adjusted
for administration of one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the pressure exerted
on a substrate is increased or decreased in order to adjust the
rate of melting, sublimation, evaporation, transformation,
activation, etc. of the one or more frozen particle compositions,
or frozen piercing implements or a component thereof. In one
embodiment, the at least one substrate includes at least one
polymer or hydrogel.
In one embodiment, the at least one agent is delivered to a single
biological cell or tissue. In one embodiment, the at least one
substrate is ingested by at least one subject.
In one embodiment, the at least one substrate includes at least one
implantable or transplantable substrate. In one embodiment, the at
least one substrate is transplanted or implanted into at least one
subject. In one embodiment, the substrate includes at least one
biological tissue from at least one donor or recipient. In one
embodiment, the at least one substrate includes at least a portion
of at least one subject. In certain embodiments, administering at
least one frozen particle composition or frozen piercing implement
includes self-administering the at least one frozen piercing
implement by the at least one subject.
In one embodiment, the at least one biological tissue includes one
or more of a plant part, or whole plant. In one embodiment, the at
least one biological tissue includes one or more of a stalk, stem,
leaf, root, or tendril. In one embodiment, the at least one
biological tissue includes at least one of meristem tissue, plant
embryo tissue, cotyledon tissue, shoot apex tissue, scutellum
tissue, epicotyl tissue, hypocotyl tissue, stamen tissue,
receptacle tissue, anther tissue, stigma tissue, ovary tissue,
carpel tissue, endosperm tissue, or seed germ tissue. In one
embodiment, the at least one biological tissue includes transgenic
tissue. In one embodiment, the transgenic tissue includes meristem
tissue cells for later generations. Non-limiting examples of plants
that are included are cereal crops, fruits, nuts, vegetables, woody
species, ornamental flower, cash crops (e.g., tobacco), and other
plants.
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements are delivered to a substrate including
at least one food or beverage product, or other product for
consumption. In one embodiment, the at least one food product
includes one or more of an animal, plant, fungal, or other
biological food product. In one embodiment, the at least one food
product includes at least one non-biological based food product. In
one embodiment, the at least one food product includes, but not
limited to at least one of a grain product; vegetable, fruit, leaf,
stem, or other plant product; meat, milk, eggs, or other animal
product; including processed products thereof. In one embodiment,
one or more frozen particle compositions, or frozen piercing
implements are delivered to at least one of a juice, cut food
product, canned food product, pulped food product, frozen food
product, homogenized food product, sterilized food product,
dehydrated food product, or otherwise processed food product. In
one embodiment, one or more frozen particle compositions, or frozen
piercing implements include at least one component of a food
product.
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements are delivered to at least one product
for consumption. In one embodiment, the product for consumption
includes, but is not limited to at least one of a hygienic product
(e.g., toothpaste, deodorant, perfume, shampoo, soap, etc.), a
cosmetic product (e.g., lotion, lipstick, nail polish, or other
facial cosmetics, etc.).
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements are delivered to at least one outdoor or
indoor area (e.g., road surface, carpet, ice rink, garden, jungle,
etc.).
In one embodiment, the substrate includes, but is not limited to,
biological tissue as described herein. For example, biological
tissue includes soft tissues (such as connective tissue, or other
soft tissue), or hard tissues (including calcified tissues, such as
bone or teeth). In one embodiment, a cell includes, but is not
limited to, at least one of an autologous cell, allogenic,
xenogenic, stem cell, or syngenic cell. The one or more cells may
include endogenous or exogenous cells relative to a particular
subject. In one embodiment, the at least one substrate includes one
or more stem cells (e.g., hematopoietic stem cells, adipocyte stem
cells, neuronal stem cells, embryonic stem cells, hepatic stem
cells, dermal stem cells, pancreatic stem cells, stem cells related
to bone, stem cells related to muscle, or others). In one
embodiment, the substrate includes at least one wound, or cell
mass. Other examples of cells and biological tissues are described
herein at other sections.
In one embodiment, the at least one biological tissue includes but
is not limited to, one or more of cartilage, skin, scalp, hair,
nail, nail bed, teeth, eye, ear, ovary, oviduct, tongue, tonsil,
adenoid, liver, bone, pancreas, stomach, appendix, duct, valve,
smooth muscle, blood vessel, bone marrow, blood, lymph, heart,
lung, brain, breast, kidney, bladder, urethra, ureter, gall
bladder, uterus, prostate, testes, vas deferens, fallopian tubes,
large intestine, small intestine, esophagus, oral cavity, nasal
cavity, otic cavity, connective tissue, muscle tissue, or adipose
tissue. In one embodiment, the at least one tissue includes one or
more of a tendon, vein (e.g., femoral or saphenous vein), artery,
or capillary. In one embodiment, the at least one biological tissue
includes embryonic or fetal tissue. In one embodiment, the at least
one biological tissue includes a mucosal surface. In one
embodiment, the at least one biological tissue includes a plant,
animal, fungal or other food product (e.g., biological food
product). In one embodiment, the at least one biological tissue
includes meat.
In one embodiment, the treatment of at least one biological tissue
includes one or more of ossicular chain reconstruction in otlogic
surgery, nerve anastomosis (e.g. peripheral nerve anastomosis);
cerebralspinal fluid sealing in neurological repair, vascular
repair or anastomosis, ocular repair, gastrological repair,
urological repair, skin closure, bronchial repair (e.g. bronchial
stump leakage), alveolar repair, or dental fillings. In one
embodiment, the at least one biological tissue includes fetal
tissues or organs (e.g. in utero) and can include any of the
tissues or organs described herein.
In one embodiment, the at least one biological tissue is located in
at least one tissue or organ related to transplantation. In one
embodiment, transplantation includes extraction or implantation of
the at least one tissue or organ. In one embodiment, the at least
one tissue or organ related to transplantation is extracted from at
least one first biological source or subject and implanted into at
least one second biological source or subject. In one embodiment,
the at least one tissue or organ related to transplantation is
cultured prior to implantation in a subject. In one embodiment, the
tissue or organ related to transplantation is an artificial or
synthetically derived tissue or organ (e.g. a bladder, heart,
kidney, liver, pancreas, skin, eye, lung, nerve, blood vessel, and
others). In one embodiment, the tissue or organ related to
transplantation involves at least two sources (i.e. multiple
species, partially artificial or synthetic, multiple biological
cells or tissues including stem cells). In one embodiment, the at
least one tissue or organ related to transplantation includes at
least one donor or recipient tissue or organ. In one embodiment,
the at least one tissue or organ is at least partly autologous.
In one embodiment, one or more blood vessels, including at least
one of a vein, artery, or capillary is at least partially made by
utilizing one or more frozen particle compositions, or frozen
piercing implements. In one embodiment, the one or more blood
vessels include at least one vascular graft at least partially made
by utilizing one or more frozen particle compositions, or frozen
piercing implements. In one embodiment, the at least one vascular
graft includes at least one autologous component. See, for example,
McAllister et al., Abstract, Lancet, vol. 373, No. 9673, pp.
1440-1446 (2009), which is incorporated herein by reference.
In one embodiment, the at least one substrate includes at least one
cell mass. In one embodiment, the at least one cell mass includes
at least one of a scar, pore, pit, eschar, granuloma, keloid,
artheromatous plaque, abscess, pustule, scaling (e.g., psoriasis or
eczema), infected tissue, hair follicle, necrotic tissue, stratum
corneum, wrinkle, wound, tumor, skin structure, nevus, cyst,
lesion, callus, neoplastic tissue, gangrenous tissue, or cellular
deposit. In one embodiment, the at least one cell mass includes at
least one benign or malignant tumor. In one embodiment, the at
least one benign or malignant tumor relates to one or more of a
melanoma, lymphoma, leukemia, sarcoma, blastoma, or carcinoma.
In one embodiment, the at least one cell mass is related to at
least one blood clot, embolus, microorganism accumulation, blood
vessel obstruction, duct obstruction, bowel obstruction, infection,
gangrene, connective tissue destruction, tissue or organ damage,
injury, white blood cell accumulation, or cancer.
In one embodiment, the at least one substrate includes one or more
wounds. In one embodiment, the one or more wounds are located in at
least one biological tissue or organ. In one embodiment, the one or
more wounds are located in one or more of skin tissue, muscle
tissue, eye tissue, nervous tissue, peritoneal tissue, an organ,
connective tissue, neoplastic tissue, or bone tissue.
In one embodiment, the one or more wounds are located in at least
one subject. The one or more wounds include but are not limited to
at least one of an incision (including surgical incision such as
for facial or other aesthetic construction or reconstruction, or
other cranio-facial surgeries, laproscopic procedures, birthing
assistance, or other surgical procedures), fracture, irritation,
episiotomy, laceration, endovascular occlusion (e.g., aneurism),
blood vessel anastomosis, nerve repair, abrasion, cerebral spinal
fluid leak, puncture wound, penetration wound, gunshot wound,
iatrogenic wound, severing, infection, ulcer, pressure sore,
lesion, chemical burn (including but not limited to exposure to an
irritant, plant, or synthetic chemical), dental caries,
first-degree burn, second-degree burn, third-degree burn,
fourth-degree burn, fifth-degree burn, or sixth-degree burn. In
certain instances, the wound can be a result of a bite, such as a
bite from an animal, insect, or arachnid.
In one embodiment, the at least one subject includes one or more of
a vertebrate or invertebrate animal. In one embodiment, the at
least one subject includes a fungus, or plant (including crop
plants, as described herein). In one embodiment, the at least one
subject includes insect cells, insects, bacteria, algae, plankton,
or protozoa. In one embodiment, the at least one subject includes
one or more of a reptile, mammal, amphibian, bird, or fish. In one
embodiment, the at least one subject includes at least one human.
In one embodiment, the at least one subject includes at least one
of livestock, pet, zoo animal, undomesticated herd animal, wild
animal, or product animal.
In one embodiment, the at least one subject includes at least one
of a sheep, goat, frog, dog, cat, rat, mouse, vermin, monkey, duck,
horse, cow, pig, chicken, shellfish, fish, turkey, llama, alpaca,
bison, buffalo, ape, primate, ferret, wolf, fox, coyote, deer,
rabbit, guinea pig, yak, chinchilla, mink, reindeer, elk, camel,
fox, elk, deer, raccoon, donkey, or mule.
Detection Materials
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements include at least one of a polymer,
biopolymer, nanoparticle, sensor, micro-syringe, actuator, circuit,
or other detection material. Such detection materials may allow for
visualization of the one or more frozen particle compositions, or
frozen piercing implements, the administration process, or provide
other benefits (including but not limited to reinforcement,
adhesive, biological remodeling, abrasive, explosive, or
therapeutic benefits). In one embodiment, the nanoparticle includes
one or more of a nanorod, nanobone, nanocapsule, or other particle.
In one embodiment, the nanoparticle releases its payload when
exposed to an energy source, including heat or light. In one
embodiment, the nanoparticles have a time-release payload of, for
example, one or more therapeutic agents, adhesive agents,
biological remodeling agents, reinforcement agents, abrasives,
explosive materials, or other agents.
In certain instances, the detection material can be located on or
in the one or more frozen particle compositions, or frozen piercing
implements, or it can be intermixed with the one or more frozen
particle compositions, or frozen piercing implements. In certain
instances, the detection material provides a "tracer" agent that
allows for visualization of one or more locations of administration
of the at least one frozen particle composition, or frozen piercing
implement. For example, in one embodiment, the detection material
includes a particle with altered isotopes (e.g., for altering the
mass of particles as a tracer). In one embodiment, only certain
frozen particle compositions, or frozen piercing implements of a
plurality of frozen particle compositions, or frozen piercing
implements include one or more detection materials. In one
embodiment, one or more detection materials are included in one or
more frozen particle compositions, or frozen piercing implements in
a predictable or predictive manner, for example, about every
2.sup.nd, about every 3.sup.rd, about every 4.sup.th, about every
5.sup.th, about every 6.sup.th, about every 7.sup.th, about every
8.sup.th, about every 9.sup.th, about every 10.sup.th, about every
20.sup.th, about every 50.sup.th, about every 100.sup.th, about
every 1000.sup.th, about every 2000.sup.th, or about every
5000.sup.th, etc. frozen particle composition, or frozen piercing
implement includes one or more detection materials.
In certain instances the detection material is located on the at
least one frozen particle composition, or frozen piercing implement
or the at least one frozen particle. In other instances, the
detection material is separate from the at least one frozen
particle composition, or frozen piercing implement. In certain
instances, the detection material forms a mixture with the frozen
particle composition, or frozen piercing implement. In certain
instances, the detection material is separate from the one or more
frozen particle compositions, or frozen piercing implements and is
administered at approximately the same time, in approximately the
same place, or in approximately the same manner as the one or more
frozen particle compositions, or frozen piercing implements. In one
embodiment, the detection material is located in at least one
cavity or compartment of the one or more frozen particle
compositions, or frozen piercing implements.
In one embodiment, detection material includes a detection label
including but not limited to, a colorimetric label, a radioactive
label, a light-emitting label (such as a luminescent compound, a
fluorescent compound, a phosphorescent compound, or a quantum dot),
a nucleic acid label, a protein label, an antibody label, a ligand
label, a receptor label, a magnetic label, or other detection
label. In one embodiment, the at least one detection material
includes but is not limited to, at least one electronic
identification device. In one embodiment, the at least one
electronic identification device includes at least one radio
frequency identification device.
In one embodiment, the at least one detection material includes but
is not limited to, at least one radioactive element. In one
embodiment, the radioactive element includes but is not limited to,
.sup.32P, .sup.35S, .sup.13C, .sup.131I, .sup.191Ir, .sup.192Ir,
.sup.193Ir, .sup.201Tl, or .sup.3H. In one embodiment, the at least
one detection material includes at least one radioactive,
luminescent, colorimetric or odorous substance. In one embodiment,
the at least one colorimetric substance includes one or more of an
inorganic, organic, biological, natural, artificial, or synthetic
substance. The colorimetric substance may include, but not be
limited to a dye or a pigment. The colorimetric substance may
include a chromogenic substrate.
In one embodiment, the at least one detection material includes at
least one light-emitting substance, such as a luminescent
substance, a fluorescent substance, phosphorescent substance, or
quantum dot. In one embodiment, the at least one detection material
is nontoxic, biocompatible, bioresorbable, or biodegradable.
Some examples of colorimetric substances include, but are not
limited to, colored agents that have an affinity for a cell or
tissue, such as acid dyes (e.g., water-soluble anionic dyes), basic
dyes (e.g., water-soluble cationic dyes), direct or substantive
dyes (e.g., stains for nucleic acids, proteins, lipids,
carbohydrates, cell populations, tissues, or organelles), mordant
dyes, vat dyes, reactive dyes, disperse dyes, azo dyes, sulfur
dyes, food dyes, solvent dyes, carbene dyes, or others. Some
examples of chromophores that can be utilized include, but are not
limited to, dyes that are based on or derivatives of acridine,
anthraquinone, arymethane (e.g., diphenyl methane, triphenyl
methane), --N.dbd.N azo structure, phthalocyanine, diazonium salts,
--NO.sub.2 nitro functional group, --N.dbd.O nitroso functional
group, phthalocyanine, quinine, azin, eurhodin, safranin, indamin,
indophenol, oxazin, oxazone, thiazin, thiazole, xanthene, fluorine,
pyronin, fluorine, rhodamine, or others. In one embodiment, the
colorimetric substance includes trypan blue.
In one embodiment, the detection material includes at least one
light-emitting substance, including but not limited to luminescent
substances (e.g. bioluminescent substances, chemiluminescent
substances, luciferin, isoluminol, luminescent minerals, etc.). In
one embodiment, the detection material includes one or more one or
more fluorescent tags, including but not limited to fluorescein,
phycobilin, phycoerythrin, phycourobilin, chlorophyll, phycocyanin,
allophycocyanin, green fluorescent protein, or others. In one
embodiment, the at least one detection material includes but is not
limited to, at least one of a diamagnetic particle, ferromagnetic
particle, paramagnetic particle, super paramagnetic contrast agent,
particle with altered isotope, or other magnetic particle.
Some non-limiting examples of particular diamagnetic substances
include wood, water, organic compounds (such as petroleum), metals
(including copper, mercury, gold, bismuth), or benzoic acid.
Methods, Devices, Systems for Administering a Frozen Particle
Composition or Frozen Piercing Implement
As described herein, a device or machine (including a computer) may
be utilized in various aspects relating to compositions, methods,
or systems relating to one or more frozen particle compositions, or
frozen piercing implements (or the devices thereof). Non-limiting
examples of such aspects may include predicting or calculating
various properties or characteristics relating to the one or more
frozen particle compositions, or frozen piercing implements, any
substrate, any subject, any administration device, or any
administration protocol. Any method disclosed herein is implicitly
intended to also include "means for" carrying out the method. One
or more methods disclosed include computer-implemented methods.
In one embodiment, a method or means for making one or more frozen
particle compositions, or frozen piercing implements optionally
includes at least one agent. In one embodiment, a method or means
for administering or delivering one or more frozen particle
compositions, or frozen piercing implements is disclosed. In one
embodiment, a method or means for administering at least one frozen
particle composition, or frozen piercing implement includes
administering at least one agent to a substrate.
In one embodiment, the at least one agent may provide promoting
wound healing; promoting healing of skin, cartilage, or bone;
filling of skin wrinkles or flaws; filling of connective tissue;
treating vesico-ureteral reflux; treating urinary incontinence;
fixing prostheses or materials to at least one biological tissue;
or producing at least one film, gel, or membrane for use in vitro
or in vivo to assist in a biological function.
In one embodiment, a method or means for of providing at least one
agent, such as a biological remodeling agent, to at least one
substrate comprises administering one or more frozen particle
compositions to at least one substrate, wherein the one or more
frozen particle compositions, or frozen piercing implements include
at least one biological remodeling agent as described herein. In
one embodiment, the one or more frozen particle compositions, or
frozen piercing implements have one or more phases including at
least one of amorphous solid water, low density amorphous ice, high
density amorphous ice, very high density amorphous ice, clathrate
ice, hyperquenched glassy water, ice Ic, ice II, ice III, ice IV,
ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice XII,
ice XIII, ice XIV, or ice XV. In one embodiment, the one or more
frozen particle compositions, or frozen piercing implements
including one or more frozen particles and at least one agent have
one or more phases including at least one of amorphous solid water,
low density amorphous ice, high density amorphous ice, very high
density amorphous ice, clathrate ice, hyperquenched glassy water,
ice Ic, ice II, ice III, ice IV, ice V, ice VI, ice VII, ice VIII,
ice IX, ice X, ice XI, ice XII, ice XIII, ice XIV, or ice XV.
In one embodiment, a method or means for at least partially
constructing or at least partially reconstructing at least one
biological tissue or organ comprises administering one or more
frozen particle compositions, or frozen piercing implements that
include at least one agent (such as at least one of a biological
remodeling agent, adhesive agent, therapeutic agent, reinforcement
agent, abrasive, or explosive material) in such a manner that the
at least one agent is deposited. In one embodiment, the at least
one agent includes at least one biological remodeling agent.
In one embodiment, the method or means for includes abrading or
ablating one or more surfaces of the at least one substrate prior
to, during, or subsequent to the administering of the one or more
frozen particle compositions, or frozen piercing implements. In one
embodiment, the method or means for administering one or more
frozen particle compositions, or frozen piercing implements is
provided in such a manner as to induce at least one cellular event.
In one embodiment, the at least one cellular event includes one or
more of: cell migration, cell attachment, cell retention, cell
differentiation, cell proliferation, apoptosis, diffusion of
materials, angiogenesis, nucleic acid expression, protein
translation, protein modification, carbohydrate production,
carbohydrate secretion, protein secretion, fat production or fat
secretion. In one embodiment, the method further includes
administering at least one component including an optical,
photonic, or electronic article. In one embodiment, the at least
one article is configured to communicate with at least one computer
system. In one embodiment, the at least one article is configured
to monitor at least one characteristic of the at least one
biological tissue.
As described herein, in one embodiment, computer-aided tissue
engineering (CATE) is utilized in the design (including tissue
scaffold design), image processing, predicting, modeling,
simulation, manufacturing, administration or delivery of at least
one frozen particle composition, or frozen piercing implement,
informatics (including computer-aided tissue classification and
application for tissue identification and characterization at
different tissue hierarchical levels), or other aspects of tissue
reconstruction with one or more frozen particle compositions, or
frozen piercing implements described. In one embodiment,
computer-aided tissue engineering compares information regarding at
least one of design, image processing, predicting, modeling,
simulation, manufacturing, administration or delivery of at least
one frozen particle composition, or frozen piercing implement, or
informatics for at least one biological tissue with at least one
dataset or database. In one embodiment, a dataset or database is
generated from information regarding at least one of design, image
processing, predicting, modeling, simulation, manufacturing,
administration or delivery of at least one frozen particle
composition, or frozen piercing implement, informatics, or other
aspect of tissue reconstruction with one or more frozen particle
compositions, or frozen piercing implements described.
In one embodiment, ink jet printing is utilized for stereo-model
fabrication, or for direct biological tissue construction,
reconstruction, or remodeling through deposition or administration
of one or more frozen particle compositions. (See, for example,
Mironov, et al, Trends in Biotech. Vol. 21, No. 4; pp. 157-161
(2003), which is incorporated herein by reference.) In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements include one or more agents that fuse upon
administration or deposition. (See, for example, Jakab, et al,
Tissue Eng. Part A, Vol. 14, No. 3 pp. 413-421 (2008), which is
incorporated herein by reference.)
In one embodiment, at least one of rapid prototyping (including but
not limited to stereolithography), fused deposition modeling,
three-dimensional printing, selective deposition modeling, solid
free-form fabrication (SFF), selective laser sintering, laminated
object manufacturing, gas foaming, solvent casting and particulate
leaching, emulsification, freeze-drying, phase separation, shape
deposition manufacturing, or other method is utilized with
administration of one or more frozen particle compositions, or
frozen piercing implements for tissue reconstruction. (See, for
example, U.S. Patent Application Publication No. 20040075196;
Barry, et al., Phil. Trans. R. Soc. A vol. 364, pp. 249-261 (2006);
and U.S. Patent Application Publication No. 20080145639, each of
which is incorporated herein by reference.) In one embodiment, a
model is used for designing or developing the architecture of the
at least one biological tissue prior to administering or depositing
the one or more frozen particle compositions, or frozen piercing
implements for at least partially constructing, at least partially
reconstructing, or at least partially remodeling at least one
biological tissue. In one embodiment, the one or more frozen
particle compositions, or frozen piercing implements are
administered or deposited directly onto at least one substrate for
at least partially constructing, at least partially reconstructing,
or at least partially remodeling at least one biological tissue. In
one embodiment, the at least partial reconstruction, at least
partial construction, or at least partial remodeling of at least
one biological tissue includes depositing at least one agent of at
least one frozen particle composition, or frozen piercing
implement. In one embodiment, the at least partial reconstruction,
at least partial construction, or at least partial remodeling of at
least one biological tissue includes at least partially abrading or
ablating at least one surface of at least one substrate (e.g.,
biological tissue) with at least one frozen particle composition,
or frozen piercing implement.
In one embodiment, sample cells are grown ex vivo, introduced with
scaffold in the appropriate environment for cell or tissue growth
utilizing one or more frozen particle compositions, or frozen
piercing implements, and the cells implanted or transplanted into
at least one subject. (See, for example, Sun et al., Biotechnol.
Appl. Biochem. vol. 39, pp. 29-47 (2004), which is incorporated
herein by reference.)
Computer-aided tissue modeling utilized in conjunction with certain
embodiments for administration of one or more frozen particle
compositions, or frozen piercing implements includes imaging data
acquisition. For example, a medical imaging modality must be
capable of one or more of producing three-dimensional views of
anatomy, differentiating heterogenous tissue types and displaying
the vascular structure, as well as generating computational tissue
models.
In one embodiment, computer-aided tissue modeling utilized in
conjunction with certain embodiments for administration of one or
more frozen particle compositions, or frozen piercing implements
includes generating at least one of a two-dimensional plot or a
three-dimensional model. In one embodiment, a two-dimensional plot
or three-dimensional view of anatomical modeling includes one or
more of geometry, morphology, volumetric representation,
mechanical, deformation, kinematic modeling, contour-based
modeling, surface extraction, or solid modeling. In one embodiment,
anatomical modeling occurs by way of computer-assisted tomography
(CAT) or computed tomography (CT) scan, positron emission
tomography (PET) scan, magnetic-resonance imaging (MRI),
ultrasound, electrical-impedance monitoring, x-ray, microscopy,
multiphoton calcium-imaging, or other imaging technique or device.
(See, for example, Girod et al, J. Cranio-Max. Surgery vol. 29, pp.
156-158 (2001), which is incorporated herein by reference.) In one
embodiment, multiple three-dimensional images are assembled or
integrated for modeling of the tissue or organ.
Computer-aided tissue information utilized in conjunction with
administration of one or more frozen particle compositions, or
frozen piercing implements includes one or more of cell or tissue
classification, hard tissue classification, soft tissue
classification, tumor diagnosis, morphometric or cytometric
information, tumor cell detection, tissue properties, cell
aggregation, cell or tissue growth, cell to cell interaction, or
cell to tissue interaction.
In one embodiment, at least one computer system is configured to
provide one or more instructions to one or more devices for
deposition or administration of one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, at
least one device is configured to deposit or administer one or more
frozen particle compositions, or frozen piercing implements on any
x, y, or z axis. In one embodiment, the at least one computer
system provides one or more instructions for predicting,
controlling, or varying the administration of one or more frozen
particle compositions, or frozen piercing implements or deposition
of at least one agent included in the one or more frozen particle
compositions, or frozen piercing implements on any x, y, or z
location. In one embodiment, the at least one computer system
provides one or more instructions for temporal, spatial, or
regional locations for deposition or administration of one or more
frozen particle compositions, or frozen piercing implements. Other
components of the at least one computer system or device are
included in the figures as described.
Computer-aided tissue scaffold design and manufacturing utilized in
conjunction with certain embodiments for administration of one or
more frozen particle compositions, or frozen piercing implements
includes one or more of tissue scaffold modeling, biomimetic
design, tissue scaffold fabrication, hybrid scaffold and cells,
cell pattern, printing and deposition, or blueprint and organ
hierarchical modeling. For example, in one embodiment, at least one
parameter for at least partially constructing, at least partially
reconstructing, or at least partially remodeling at least one
tissue that are considered in design and administration of one or
more frozen particle compositions, or frozen piercing implements,
includes one or more of porosity, pore size, interconnectivity,
transport properties, cell-tissue formation, mechanical strength,
facilitation of attachment or distribution, growth of regenerative
tissue and facilitate the transport of nutrients or other
factors.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements are administered to at least one
substrate by way of biopolymer deposition layering. For example,
technology related to a micronozzle-based layered manufacturing, a
microsyringe-based deposition, three dimensional plotting (e.g.,
Bioplotter, Envision Tech., Marl, Germany), or micromolding (e.g.,
by vacuum-molding) are capable of being utilized with the one or
more frozen particle composition, or frozen piercing implement
deposition. (See, for example, U.S. Patent Application Publication
No. 20060195179.)
In one embodiment, the reconstructed tissue manufactured by use of
one or more frozen particle compositions, or frozen piercing
implements includes at least one material that mimics natural
structures or functions, or enhances natural tissue growth. For
example, in one embodiment, one or more frozen particle
compositions, or frozen piercing implements are included in "smart"
tissue scaffolds including one or more of a sensor, syringe,
therapeutic agent, electronic article, nano-scale device,
micro-scale device, or feedback mechanism. For example, at least
one biosensor, circuit, or other electronic article can be included
for monitoring tissue growth, dissolution, deterioration,
biochemical function, structural integrity or function,
immunological reaction, or other activities or conditions; or for
providing a feedback mechanism. In one embodiment, the at least one
optical, photonic, or electronic article included in the at least
one tissue or organ is capable of communicating with at least one
computer system.
In addition, one or more agents are included in one embodiment of
the tissue reconstructed with one or more frozen particle
compositions, or frozen piercing implements. Such agents include at
least one of a therapeutic agent, abrasive, explosive material,
adhesive agent, reinforcement agent, biological remodeling agent,
one or more cells, or other agent. In one embodiment, the
reconstructed or remodeled tissue includes at least one
gene-activated matrix that allows for incorporation of one or more
specific genes when one or more cells are administered to the
matrix, or are allowed to migrate to the matrix. In one embodiment,
one or more frozen particle compositions, or frozen piercing
implements are utilized in three-dimensional cell or organ
printing.
As described herein, in one embodiment the at least one biological
remodeling agent includes one or more of: scaffolding materials,
cells, nutrients, growth factors, or other components for at least
partially constructing at least one tissue or organ de novo. See
Sun, et al, Ibid.
In one embodiment, a scaffold is constructed, at least in part by
seeding living cells into the scaffold. As described herein,
various materials are capable of being utilized as a scaffold by
delivering one or more frozen particle compositions, or frozen
piercing implements, or deposition of at least one agent included
in one or more frozen particle compositions, or frozen piercing
implements. In particular, materials including but not limited to,
pastes, resins, gels, bone cements, cellulose, silicone,
polyurethanes, hydrogels, chitosan, or ceramic powders can be
used.
Also as described herein, one or more materials utilized for the
scaffold can be used for cell seeding, delivery systems for one or
more therapeutic agents, other agents, or for integrating one or
more angiogenic factors, growth factors, cytokines, or other
agents.
In one embodiment, a composition includes an ex vivo biological
tissue or organ that is at least partially constructed or at least
partially reconstructed by administering one or more frozen
particle compositions, or frozen piercing implements. In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements include at least one of a therapeutic agent,
adhesive agent, biological remodeling agent, explosive material,
abrasive, or reinforcement agent.
In one embodiment, the ex vivo biological tissue or organ is at
least partially constructed or at least partially reconstructed de
novo by administering one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the one or more
frozen particle compositions, or frozen piercing implements are
administered to at least one substrate. In one embodiment, the at
least one substrate includes one or more of a cell, tissue, organ,
structure, or device. In one embodiment, the composition further
includes at least one article including an optical, photonic, or
electronic article. In one embodiment, the at least one article is
configured to communicate with at least one computer system. In one
embodiment, the at least one article is configured to monitor at
least one characteristic of the at least one biological tissue or
organ. In one embodiment, the at least one characteristic of the at
least one biological tissue or organ includes one or more of:
tissue formation, tissue growth, cell proliferation, cell
differentiation, apoptosis, dissolution, deterioration, nuclear
division, biochemical function of at least one cell, biochemical
function of at least one tissue, biochemical function of at least
one organ, structural integrity, structural function, immunological
reaction, or durability of the at least one biological tissue or
organ. In one embodiment, the at least one characteristic of the at
least one biological tissue or organ includes one or more of:
tissue formation associated with at least one substrate, tissue
growth associated with at least one substrate, cell proliferation
associated with at least one substrate, cell differentiation
associated with at least one substrate, apoptosis associated with
at least one substrate, dissolution associated with at least one
substrate, deterioration associated with at least one substrate,
biochemical function of at least one cell or tissue associated with
at least one substrate, structural integrity of at least one
substrate, structural function of at least one substrate,
immunological reaction to at least one substrate, or durability of
at least one substrate.
In one embodiment, a composition comprises a support means for
aiding in at least partially constructing or at least partially
reconstructing at least one biological tissue or organ; and one or
more frozen particle compositions, or frozen piercing implements as
described herein. In one embodiment, the one or more frozen
particle compositions, or frozen piercing implements include at
least one biological remodeling agent, adhesive agent, explosive
material, abrasive, reinforcement agent, or therapeutic agent. In
one embodiment, the support means includes at least one substrate
configured for biological tissue formation or tissue growth. In one
embodiment, the support means includes one or more of a cell
scaffold, a tissue scaffold, extracellular matrix, methylcellulose,
agarose, cellulose, a cell, a polymer, or other substrate. In one
embodiment, the support means includes at least one substrate
configured for promoting one or more of: cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
protein secretion, carbohydrate production, carbohydrate secretion,
fat production, or fat secretion.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements are deposited on a pre-existing
substrate scaffolding, such as a flat or honeycomb film. See, for
example, Nishikawa et al., Mat. Res. Soc. Symp. Proc. Vol. 724 pp,
N11.7.1-N 11.7.6 (2002). In one embodiment, at least one agent
included in one or more frozen particle compositions, or frozen
piercing implements are deposited such that the scaffolding is
formed entirely from such deposition.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements include one or more cells. In one
embodiment, the one or more cells are deposited during
administration of the one or more frozen particle compositions, or
frozen piercing implements. In one embodiment, the one or more
frozen particle compositions, or frozen piercing implements are
administered to at least one substrate. In one embodiment, the one
or more cells serve particular functions. In one embodiment, the
one or more cells serve at least one function including: seeding
the scaffold, populating the tissue, reducing an immune reaction,
facilitating tissue function, promoting cellular or tissue
formation, promoting cellular or tissue proliferation, promoting
cellular or tissue differentiation, promoting cellular or tissue
apoptosis, modulating diffusion of materials, or increasing tissue
growth.
In one embodiment, at least one scaffold, or other substrate is at
least partially generated in at least one of in vitro, in vivo, ex
vivo, in utero, or in planta. In one embodiment, one or more cells
are utilized for seeding at least one scaffold in at least one of
in vitro, in vivo, ex vivo, in utero, or in planta. In one
embodiment, the scaffold or other substrate is at least partially
generated in at least one of in vitro, in vivo, ex vivo, in utero,
or in planta, and subsequently is transplanted or implanted into at
least one subject. In one embodiment, the subject includes the same
subject in which the scaffold or other substrate was at least
partially generated. In one embodiment, wherein the scaffold or
other substrate is transplanted or implanted, the scaffold or other
substrate is modified in vitro, in vivo, ex vivo, in utero, or in
planta prior to transplantation or implantation into at least one
subject. In one embodiment, the at least one scaffold or at least
one remodeled or reconstructed tissue is transplanted or implanted
one or more times. In at least on embodiment, at least one
substrate, including at least one tissue scaffold, is at least
partially generated in vivo, and subsequently relocated within the
same subject. (See, for example, Ripamonti et al., J. Anat. Vol.
209, pp. 447-468 (2006), which is incorporated herein by
reference.)
In one embodiment, construction, reconstruction, or remodeling of
at least one biological tissue or organ includes at least one of
designing a blueprint or model. In one embodiment, the blueprint or
model includes a software representation containing
bio-information, graphical representation, physical or material
information, or anatomic or geometric information. In one
embodiment, the blueprint or model includes a process model,
including a software representation that contains the printing
operation control commands, process planning, or toolpath generated
for the blueprint or model and machine hardware and control system.
In one embodiment, the blueprint or model includes a process
machine, including at least one of a hardware representation that
is capable of printing; and a tissue or organ culture system that
is capable of maintaining or growing the printed living biological
tissues. In one embodiment, the three dimensional organ or tissue
printing with one or more frozen particle compositions, or frozen
piercing implements includes at least one of pre-processing or
developing plots or blueprints for the tissue or organ; processing
or actual organ printing; or post-processing or organ conditioning
and accelerated organ maturation.
In one embodiment, the blueprint or model includes a description or
representation of details of organ anatomy, morphology, tissue
heterogeneity, or vascular systems at different tissue or organ
organizational scales. In one embodiment, deposition of at least
one tissue remodeling agent includes a process planning program
control system. In one embodiment, a toolpath program is included.
In certain instances, the blueprint or model provides at least one
description of the anatomy, geometry, internal architecture of an
organ or tissue of interest (including tissue heterogeneity),
individual tissue geometry and boundary distinction within the
tissue or organ of interest; at least one definition of vascular
networks and three dimensional topology in an organ of interest; or
at least one database of information based on organ or tissue
geometry, heterogeneity, and vascular network used for toolpath or
other program generation of three-dimensional cell or organ
printing.
In one embodiment, the blueprint or model is constructed from three
dimensional organ anatomy, tomography, or geometry information
provided by medical imaging data (for example, as provided for by
CT, PET, MRI, ultrasound, x-ray, multiphoton calcium-imaging, or
other imaging). Such images can be modified, simulated,
transformed, processed (e.g., electronically processed), or modeled
by a computer system, including by computer program, such as NURBS,
polygonal modeling, or splines and patches modeling. (See, for
example, Sun et al, Ibid.) For example, Boolean, scaling, Gaussian
smoothing, homomorphic filtering, parametric estimation techniques,
Monte Carlo simulations, wavelet based methods, smoothing,
mirroring, gradient weighted partial differential equation
smoothing (PDE), or other operations can be used to modify a CAD or
other design. (See, for example, U.S. Patent Application
Publication No. 20060233454, and U.S. Pat. Nos. 7,353,153,
7,212,958; each of which is incorporated herein by reference.) In
one embodiment, a computer system utilized in at least partial
tissue construction, reconstruction, or remodeling includes at
least one software program interface to convert the CAD design or
device into a heterogeneous material or assembly for formation of
the tissue or organ by deposition of at least one agent included in
one or more frozen particle compositions, or frozen piercing
implements, or administration of one or more frozen particle
compositions, or frozen piercing implements. (See, for example,
U.S. Patent Application Publication No. 20060105011, which is
incorporated herein by reference.) In one embodiment, processing
results include utilizing one or more of algorithmic execution,
logical decision-making, or result prediction.
In one embodiment, one or more adjacent areas of constructed or
reconstructed tissues or organs include similar biological
remodeling agents. In one embodiment, one or more adjacent areas of
constructed or reconstructed tissues or organs include different
biological remodeling agents. In one embodiment, one or more
substrate scaffolds are utilized to at least partially construct,
at least partially reconstruct, or at least partially remodel at
least one tissue or at least one organ. In one embodiment, the one
or more substrate scaffolds include low microporosity, for strong
structural or mechanical load, while one or more adjacent areas
include high microporosity as well as embedded angiogenic factors,
cytokines, cells, or other agents for seeding the structural
component(s).
In one embodiment, three-dimensional CAD based models of the
desired tissue are capable of being modified by Boolean operations,
or separated into components or elements that each are
independently exportable to freeform-fabrication technologies. In
one embodiment, heterogeneous blocks are assembled brick-like into
a tissue or organ. In one embodiment, solid structural models are
manufactured out of substrate materials including for example,
quartz or Teflon.RTM.. The models are then infiltrated with
vasculature, living tissue, cells, or other agents. (See, for
example, Sun et al, Ibid.)
In one embodiment, a method or means for performing the same
includes accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed;
accepting a second input associated with at least one parameter of
at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions, or frozen piercing
implements including at least one agent; and processing results of
the first input and the second input. In one embodiment, the method
or means for performing the method is implemented by a computer,
including a computer system.
In one embodiment, the processing results of the first input and
the second input includes electronically processing results of the
first input and the second input. In one embodiment, the processing
results of the first input and the second input includes
electronically processing results of the first input and the second
input by utilizing one or more of Gaussian smoothing, scaling,
homomorphic filtering, parametric estimation techniques, Boolean
operations, Monte Carlo simulations, wavelet based techniques,
mirroring, smoothing, gradient weighted partial differential
equation smoothing, NURBS, polygonal modeling, algorithmic
execution, logical decision-making, result prediction, splines and
patches modeling, or modification of a CAD design.
In one embodiment, the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment, the administering one or more frozen particle
compositions, or frozen piercing implements includes administering
the one or more frozen particle compositions, or frozen piercing
implements to at least one substrate. In one embodiment, the at
least one substrate includes one or more of a cell, tissue, organ,
structure, or device.
In one embodiment, the first input includes one or more values
related to the at least one characteristic of at least one
biological tissue. In one embodiment, the first input includes one
or more spatial addresses associated with the at least one
characteristic of at least one biological tissue. In one
embodiment, the first input includes one or more of x, y, or z
coordinates associated with the at least one characteristic of at
least one biological tissue. In one embodiment, the at least one
characteristic of at least one biological tissue to be constructed
or reconstructed includes one or more of: morphological feature,
anatomical feature, histological feature, tissue hierarchical
level, scaffold feature, vascular structure feature, heterogenous
tissue feature, mechanical feature, volumetric feature, geometric
feature, volumetric representation, mechanical feature,
deformation, kinematic feature, surface contour feature, cytometric
feature, cell aggregation, cell growth, cell-cell interaction,
cell-tissue interaction, biomimetic design, cell pattern, cell
deposition, organ hierarchical level, tissue microstructure,
cellular microstructure, cell junction feature, tissue junction
feature, cell-tissue classification, hard tissue classification,
soft tissue classification, tumor diagnosis, or other feature.
In one embodiment, the first input includes one or more temporal
addresses associated with the at least one characteristic of at
least one biological tissue. In one embodiment, the first input
includes one or more values derived from at least one image of the
at least one biological tissue. In one embodiment, the at least one
image includes one or more images acquired by one or more of laser,
holography, x-ray crystallography, optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, electrical-impedance monitoring, microscopy, spectrometry,
flow cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation.
In one embodiment, the at least one characteristic of at least one
biological tissue includes one or more of cellular type, cellular
function, cellular size, cellular constitution, cellular
architecture, cellular durability, cellular source, tissue type,
tissue constitution, tissue size, tissue shape, tissue function,
tissue architecture, tissue source, tissue durability, organ type,
organ constitution, organ size, organ shape, organ function, organ
architecture, organ source, or organ durability. In one embodiment,
the at least one biological tissue is located in at least one of in
situ, in vitro, in vivo, in utero, in planta, in silico, or ex
vivo. In one embodiment, the at least one biological tissue is at
least partially located in at least one subject.
In one embodiment, the method or means for performing the method
further comprises accepting a third input associated with at least
one feature of the at least one subject. In one embodiment, the at
least one feature of the at least one subject includes one or more
of age, gender, genotype, phenotype, proteomic profile, or health
condition.
In one embodiment, the first input includes one or more values
derived from at least one image of the at least one biological
tissue at least partially located in at least one subject. In one
embodiment, the processing results of the first input and the
second input includes determining at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue with one or more frozen particle
compositions, or frozen piercing implements from one or more values
derived from at least one image of the at least one biological
tissue.
In one embodiment, the second input includes one or more values
related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions, or frozen piercing implements to the at least one
substrate. In one embodiment, the at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue includes one or more of porosity
of the at least one substrate, pore size of the at least one
substrate, interconnectivity of the pores of the at least one
substrate, transport properties of the at least one substrate,
cell-tissue formation of the at least one substrate, mechanical
strength of the at least one substrate, ability for attachment or
distribution of the at least one agent included in the one or more
frozen particle compositions, or frozen piercing implements to the
at least one substrate, ability for attachment or distribution of
one or more cells or tissues to the at least one substrate,
facilitation of at least one nutrient, or tissue formation or
tissue growth associated with the at least one substrate.
In one embodiment, the one or more values related to the at least
one parameter of constructing or reconstructing the at least one
biological tissue includes one or more predictive values. In one
embodiment, the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions, or frozen piercing implements includes one or more of
design of plot or model for administration of one or more frozen
particle compositions, or frozen piercing implements, constitution
of the one or more frozen particle compositions, or frozen piercing
implements, formulation of the one or more frozen particle
compositions, or frozen piercing implements, size of the one or
more frozen particle compositions, or frozen piercing implements,
shape of the one or more frozen particle compositions, or frozen
piercing implements, angle of administration of the one or more
frozen particle compositions, or frozen piercing implements,
velocity of administration of the one or more frozen particle
compositions, or frozen piercing implements, quantity of frozen
particle compositions, or frozen piercing implements administered,
rate of administration of more than one frozen particle
composition, spatial location for administration of one or more
frozen particle compositions, or frozen piercing implements,
temporal location for administration of one or more frozen particle
compositions, or frozen piercing implements, method or means for
administration of one or more frozen particle compositions, or
frozen piercing implements, timing of administration of one or more
frozen particle compositions, or frozen piercing implements,
modulation of administration of one or more frozen particle
compositions, or frozen piercing implements, deposition of one or
more frozen particle compositions, or frozen piercing implements,
or rate of deposition of at least one agent.
In one embodiment, the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions, or frozen piercing implements includes at least one
parameter relating to at least partially ablating or at least
partially abrading one or more surfaces of the at least one
biological tissue with the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
at least one parameter of at least partially constructing or at
least partially reconstructing the at least one biological tissue
by administering one or more frozen particle compositions, or
frozen piercing implements includes at least one parameter relating
to administering at least one of a therapeutic agent, adhesive
agent, biological remodeling agent, reinforcement agent, abrasive,
or explosive material with the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
spatial location for administration of one or more frozen particle
compositions, or frozen piercing implements includes one or more of
x, y, or z coordinates.
In one embodiment, the processing results includes comparing at
least one value related to the first input associated with the at
least one characteristic of at least one biological tissue to be at
least partially constructed or at least partially reconstructed
with at least one value related to at least one image of a target
biological tissue. In one embodiment, the image of a target
biological tissue includes an image of a similar biological tissue,
or an image of a dissimilar biological tissue. In one embodiment,
administering one or more frozen particle compositions, or frozen
piercing implements includes depositing the at least one agent on
the at least one substrate. In one embodiment, processing results
includes comparing at least one value related to the second input
associated with the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue with at least one value related to another
administration of one or more frozen particle compositions, or
frozen piercing implements.
In one embodiment, processing results includes determining one or
more differences in at least one value related to the first input
and at least one value related to at least one image of the at
least one biological tissue or a similar biological tissue. In one
embodiment, processing results includes determining one or more
differences in at least one value related to the second input
associated with the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue and at least one value related to another
administration of one or more frozen particle compositions, or
frozen piercing implements to the at least one substrate. In one
embodiment, processing results includes generating one or more
protocols for administering the one or more frozen particle
compositions, or frozen piercing implements. Other related
embodiments are described in detail herein.
As described herein, at least one frozen particle composition or
therapeutic composition described herein is useful in one or more
methods or means for performing the method(s), including one or
more of a method for abrasion of at least one biological tissue
surface of a subject by delivering at least one composition to at
least one surface of at least one biological tissue of a subject in
a manner sufficient to abrade the at least one surface of the at
least one biological tissue; a method of delivering at least one
therapeutic agent to at least one biological tissue; a method of
vaccinating a subject; a method of treating a tissue related to
transplantation; a method for cleaning one or more wounds; a method
for oxygenating wounds; a method for debridement of tissue or
cells; a method for removing material from one or more blood
vessel, and others. These and other methods include utilizing one
or more composition or therapeutic composition described
herein.
In one embodiment, a method of providing at least one agent to at
least one biological tissue of a subject comprises administering at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device to at least one biological
tissue, wherein the at least one frozen particle composition,
frozen piercing implement, or frozen piercing implement device
includes one or more frozen particles defining at least one cavity
and at least one agent; and the at least one cavity containing at
least one agent.
In one embodiment, a method of vaccinating a subject comprises
administering to at least one biological tissue of a subject at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device, wherein the at least one
frozen particle composition, frozen piercing implement, or frozen
piercing implement device includes one or more frozen particles
defining at least one cavity; the at least one cavity containing at
least one vaccine. In one embodiment, a method of vaccinating at
least one substrate, such as a biological tissue, includes
administering to the substrate at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device, wherein the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device includes one or more frozen particles defining at
least one cavity; the at least one cavity containing at least one
vaccine.
In one embodiment, a method of providing at least one frozen
particle composition or frozen piercing implement to at least one
biological tissue of a subject comprises administering at least one
frozen particle composition or frozen piercing implement to at
least one biological tissue, wherein the at least one frozen
particle composition or frozen piercing implement includes one or
more frozen particles including at least one cavity configured for
holding at least one agent.
In one embodiment, a method for abrasion of at least one biological
tissue surface of a subject includes delivering at least one
composition (frozen particle composition, frozen piercing
implement, etc.) to at least one surface of at least one biological
tissue of a subject in a manner sufficient to abrade the at least
one surface of the at least one biological tissue. As discussed
herein, particular methods are disclosed for abrading or ablating
at least one surface of at least one biological tissue.
In one particular example, skin abrasion for superficial
resurfacing (e.g., microdermabrasion) can be used to treat acne,
scars, hyperpigmentation, and other skin blemishes, as described
herein. Microscissuining creates microchannels in the skin by
eroding the outer layers of skin with sharp microscopic metal
granules (Carlisle Scientific, Carlisle, MA), and Med Pharm Ltd
(Charlbury, UK) has developed a novel dermal abrasion device (D3S)
for the delivery of difficult to formulate therapeutics ranging
from hydrophilic low molecular weight compounds to other
biopharmaceuticals, and can be utilized in conjunction with
administration of at least one composition described herein. See
e.g., Roberts, et al., Clin. Exp. Pharmacol. Physiol. vol. 24, pp.
874-9 (1997); Murthy, et al., J. Controlled Rel. vol. 93, pp. 49-57
(2003); each of which is incorporated herein by reference.
Abrading at least one surface of at least one biological tissue may
entail debridement of at least one biological tissue. In certain
instances, debridement may include removal or destruction of dead,
damaged, or infected cells or tissues. In certain instances,
debridement can be included as part of an additional course of
treatment (e.g., surgery). In one embodiment, debridement may
include penetrating one or more healthy cells or tissues in order
to facilitate healing. In one embodiment, debridement may include
penetrating one or more healthy cells or tissues near in proximity
to one or more unhealthy cells or tissues of a subject.
In one embodiment, one or more of the debridement methods described
herein include penetrating one or more cells or biological tissues
of a subject with at least one frozen particle composition, frozen
piercing implement (or therapeutic composition), wherein the one or
more cells or tissues are chemically or physically partitioned or
segregated from at least one other part of the tissue or another
tissue. In one embodiment, a method for debridement of at least one
biological tissue of a subject includes delivering at least one
frozen particle composition, frozen piercing implement, or
therapeutic composition to at least one biological tissue of a
subject wherein the at least one biological tissue is partitioned
from another biological tissue or part of another biological
tissue, and at least one frozen particle composition, frozen
piercing implement, or therapeutic composition penetrates the at
last one biological tissue with or without removing any tissue.
As described herein, in certain instances, a therapeutic agent is
included with the at least one frozen particle composition to form
a therapeutic composition, as described herein. In certain
instances, one or more reinforcement agents or one or more
explosive materials can be included in the at least one frozen
particle composition or therapeutic composition.
In one embodiment, a method for removing one or more materials from
at least one biological tissue includes delivering or administering
at least one frozen particle composition, frozen piercing
implement, frozen piercing implement device, or therapeutic
composition to the at least one biological tissue. In one
embodiment, the at least one biological tissue includes one or more
tissues described herein. In one embodiment, the one or more
materials may include one or more materials described herein.
In one embodiment, a method for removing one or more materials from
at least one blood vessel of at least one subject includes
delivering at least one composition to at least one blood vessel of
a subject in a manner sufficient to remove one or more
materials.
In certain instances, a method for abrasion of at least one
biological tissue or organ surface related to transplantation is
included. In one embodiment, the at least one biological tissue or
organ includes one or more of the biological tissues or organs
described herein.
In one embodiment, delivering at least one composition to at least
one surface of at least one biological tissue of a subject includes
contacting the at least one surface of at least one biological
tissue of a subject with the composition. In one embodiment,
delivering at least one composition to at least one surface of at
least one biological tissue of a subject includes contacting the at
least one surface of at least one biological tissue of a subject
with the one or more frozen particle compositions, or frozen
piercing implements. In one embodiment, delivering at least one
composition to at least one surface of at least one biological
tissue of a subject includes rupturing one or more cells of at
least one surface of at least one biological tissue of a subject
with the one or more frozen particle compositions, or frozen
piercing implements.
In one embodiment, a method described herein includes extracting or
collecting material from the at least one abraded surface of at
least one biological tissue. Such extraction or collection may
include the use of at least one vacuum, aspirator, container,
instrument, tool, device, chemical, laser, stylet, cannula, light
source, scope (e.g., laprascope), needle, scalpel, shunt, stent,
bag, film, filter, suction apparatus, tube, compressed gas, fluid
(e.g., fluid stream or mist), magnifying apparatus; imaging device,
vapor deposition, film deposition, computing device, or system.
In one embodiment, at least one of the needle, scalpel, or other
tools or instruments utilized in extracting or collecting material
from the at least one cell, tissue, or subject, includes one or
more frozen particle compositions, or frozen piercing implements
(e.g., frozen hydrogen oxide, or other agents as described herein).
Thus, the one or more frozen particle compositions, or frozen
piercing implements are fashioned or molded for use as microneedles
or other instruments (e.g., scapels, blades, tools, etc.). In one
embodiment, the one or more frozen particle compositions, or frozen
piercing implements are administered prior to, during, or
subsequent to surgery. In one embodiment, the one or more frozen
particle compositions, or frozen piercing implements are
administered during surgery, and just prior to closing the surgical
setting.
In one embodiment, the extracted or collected material includes at
least one organic or inorganic material. In one embodiment, the
material includes one or more cells from the at least one abraded
surface of at least one biological tissue. In one embodiment, the
at least one material includes at least part of a: cell, granuloma,
eschar, callus, atheromatous plaque, abscess, pustule, infected
tissue, scaling, microorganism, blood clot, embolus, blood vessel
obstruction, duct obstruction, bowel obstruction, necrotic tissue,
stratum corneum, hair follicle, nevus, wrinkle, keloid, biofilm,
calculus, plaque, tartar, dandruff, keratin, collagen, dust, dirt,
metal, glass, hair or fur, cellular secretion, microorganism, blood
cell, blood gas, blood component, organelle, cell membrane, cell
nucleus, particulate matter, or connective tissue.
In one embodiment, the at least one material includes at least one
of: enzyme, acid, amino acid, peptide, polypeptide, protein,
oligonucleotide, nucleic acid, ribonucleic acid, oligosaccharide,
polysaccharide, glycopeptide, glycolipid, lipoprotein,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood plasma, cell wall,
hormone, organic compound, inorganic compound, salt, or cell
ligand.
In one embodiment, the at least one material includes at least one
of: glucose, lactate, urea, uric acid, glycogen, oxygen, carbon
dioxide, carbon monoxide, ketone, nitric oxide, nitrous oxide,
alcohol, alkaloid, opioid, cannabinol, endorphin, epinephrine,
dopamine, serotonin, nicotine, amphetamine, methamphetamine,
anabolic steroid, hydrocodone, hemoglobin, heparin, clotting
factor, tumor antigen, pH, albumin, ATP, NADH, FADH.sub.2,
pyruvate, sulfur, mercury, lead, creatinine, cholesterol,
alpha-fetoprotein, chorionic gonadotropin, estrogen, progesterone,
testosterone, thyroxine, melatonin, calcitonin, antimullerian
hormone, adiponectin, angiotensin, cholecystokinin,
corticotrophin-releasing hormone, erythropoietin, bilirubin,
creatine, follicle-stimulating hormone, gastrin, ghrelin, glucagon,
gonadotropin-releasing hormone, inhibin, growth hormone, growth
hormone-releasing hormone, insulin, human placental lactogen,
oxytocin, orexin, luteinizing hormone, leptin, prolactin,
somatostatin, thrombopoietin, cortisol, aldosterone, estradiol,
estriol, estrone, leukotriene, brain natriuretic peptide,
neuropeptide Y, histamine, vitamin, mineral, endothelin, renin,
enkephalin, DHEA, DHT, alloisoleucine, toxic substance, illegal
substance, therapeutic agent, or any metabolite thereof.
As indicated herein, in one embodiment, a method for providing at
least one therapeutic agent to at least one biological tissue of a
subject is included. In one embodiment, the at least one
therapeutic agent is delivered to at least one biological tissue
prior to, during, or subsequent to surgery. In certain instances,
at least one therapeutic agent includes one or more therapeutic
agents described herein. In one embodiment, a method of providing
at least one therapeutic agent to at least one biological tissue of
a subject includes delivering at least one composition to at least
one biological tissue, including one or more frozen hydrogen oxide
particles including at least one therapeutic agent; wherein the at
least one composition has at least one crystalline or amorphous
phase.
As disclosed herein for other embodiments, a method of vaccinating
a subject includes administering at least one composition that
includes at least one vaccine, as well as one or more abrasives,
one or more reinforcement agents, or one or more explosive
materials. In one embodiment, the vaccine described herein relates
to a therapeutic or prophylactic vaccine, and in certain instances
the vaccine relates to an anti-cancer vaccine. In one embodiment,
the one or more abrasives are the same as the one or more
reinforcement agents, or the one or more explosive materials. In
one embodiment, the one or more abrasives are different than the
one or more reinforcement agents. In one embodiment, the one or
more abrasives are different than the one or more explosive
materials.
In certain instances, for example with at least one vaccine
composition or method relate to vaccinating wildlife animals (e.g.
vaccinating raccoons for rabies, or bison for brucellosis). In
certain instances, the vaccine compositions, and methods described
herein relate to vaccinating domesticated animals (such as cattle,
horses, sheep, or goats). In certain instances, vaccine
compositions and methods described herein relate to vaccinating a
group of subjects, such as a population, a herd, a pride, a gaggle,
a pack, flock, band, cluster, school, brood, troop, colony, or
other group. In certain instances, vaccinating a group of subjects
is included as a route to regulate or control infection within a
group of subjects.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements are delivered or administered to the at
least one substrate, such as at least one biological tissue, in a
directed manner such that the tissue is etched, tattooed, shaped,
carved, or otherwise modified. In one embodiment, the directed
manner is predetermined based on information, such as from the at
least one biological tissue, the subject, the at least one frozen
particle composition, the context of the debridement, the health of
the biological tissue, the health of the subject, or other
information.
Frozen Piercing Implements
In one embodiment, a frozen piercing implement includes one or more
means for piercing at least one substrate, means for delivering at
least one agent to at least one substrate, or means for sensing or
extracting at least one material from at least one substrate.
In one embodiment, the frozen piercing implement comprises a
sterile frozen hydrogen oxide implement configured for piercing at
least part of at least one substrate.
In one embodiment, the sterile frozen hydrogen oxide is
substantially in one or more phases including at least one of
amorphous solid water, low density amorphous ice, high density
amorphous ice, very high density amorphous ice, clathrate ice,
hyperquenched glassy water, ice Ic, ice Ih, ice II, ice III, ice
IV, ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice
XII, ice XIII, ice XIV, or ice XV.
In one embodiment, the frozen piercing implement includes at least
one sterile frozen solution, the solution including at least one
agent; wherein the frozen piercing implement is configured for
piercing at least part of at least one substrate.
In one embodiment, the frozen piercing implement includes at least
one non-hydrogen oxide frozen solvent; wherein the frozen piercing
implement is configured for piercing at least one substrate; and
wherein the frozen piercing implement is substantially solid at
approximately 65.degree. C., approximately 60.degree. C.,
approximately 55.degree. C., approximately 50.degree. C.,
approximately 45.degree. C., approximately 40.degree. C.,
approximately 37.degree. C., approximately 35.degree. C.,
approximately 30.degree. C., approximately 25.degree. C.,
approximately 20.degree. C., approximately 15.degree. C.,
approximately 10.degree. C., approximately 5.degree. C.,
approximately 0.degree. C., approximately -5.degree. C.,
approximately -10.degree. C., approximately -15.degree. C.,
approximately -20.degree. C., approximately -25.degree. C.,
approximately -30.degree. C., approximately -40.degree. C.,
approximately -50.degree. C., approximately -60.degree. C.,
approximately -70.degree. C., approximately -80.degree. C.,
approximately -90.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -170.degree. C., approximately -200.degree. C.,
approximately -250.degree. C., or any temperature therebetween. In
one embodiment, the at least one non-hydrogen-oxide frozen solvent
includes at least one of acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, acetonitrile, hexane,
dichloromethane, methylene chloride, carboxylic acid, saline,
standard saline citrate, methane, toluene, chloroform, or diethyl
ether. In one embodiment, the frozen piercing implement further
comprises at least one of polyethylene glycol, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, HEPES-buffered saline, dextrose, or glucose.
In one embodiment, the frozen piercing implement, comprises: at
least one sterile frozen component and at least one agent; wherein
the at least one component is substantially in a gaseous state at
or above approximately 0.25 bar, approximately 0.5 bar,
approximately 1.0 bar, approximately 5.0 bar, approximately 10.0
bar, approximately 25 bar, approximately 50 bar, approximately 100
bar, approximately 200 bar, or approximately 500 bar pressure; and
at or above approximately 10.degree. C., approximately 15.degree.
C., approximately 20.degree. C., approximately 25.degree. C.,
approximately 30.degree. C., approximately 37.degree. C.,
approximately 40.degree. C., approximately 45.degree. C., or
approximately 50.degree. C.; and wherein the at least one frozen
piercing implement is configured for piercing at least one
substrate. In one embodiment, the at least one component includes
one or more of nitrogen, helium, neon, xenon, oxygen, air, krypton,
chlorine, bromine, or argon.
In one embodiment, the frozen piercing implement has at least one
major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer, or any value therebetween. In
one embodiment, the frozen piercing implement is substantially in
the form of one or more frozen particles. In one embodiment, the at
least one major dimension includes at least one of a radius,
diameter, length, width, height, or perimeter.
In one embodiment, the frozen piercing implement is configured for
delivering at least one agent to the at least one substrate. As
described herein, the at least one agent includes at least one of a
therapeutic agent, explosive material, reinforcement agent,
adhesive agent, biological remodeling agent, or abrasive. In one
embodiment, the at least one agent includes at least one of a
nontoxic, biocompatible, bioresorbable, or biodegradable agent. In
one embodiment, the at least one agent includes at least one
sterile or sterilizing agent. In one embodiment, the at least one
sterilizing agent includes at least one antimicrobial compound. In
one embodiment, the at least one sterilizing agent includes at
least one antiseptic. In one embodiment, the at least one agent is
included as an outer coating of the frozen piercing implement. In
one embodiment, the at least one agent is encapsulated within the
frozen piercing implement. In one embodiment, the at least one
agent is included as part of a carrier that assists in synthesis or
activation of the at least one agent. In one embodiment, the at
least one agent includes one or more components that are inactive.
In one embodiment, the one or more components are configured to be
activated by administration. In one embodiment, the at least one
agent includes one or more of a prodrug or precursor compound.
In one embodiment, the frozen piercing implement is substantially
solid at approximately 0.degree. C., approximately -10.degree. C.,
approximately -20.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -75.degree. C., approximately -80.degree. C.,
approximately -85.degree. C., approximately -90.degree. C.,
approximately -95.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -180.degree. C., approximately -200.degree. C.,
approximately -220.degree. C., approximately -250.degree. C., or
any temperature less than or therebetween.
In one embodiment, the frozen piercing implement includes at least
one cavity. In one embodiment, at least one agent is located in the
at least one cavity. In one embodiment, the frozen piercing
implement includes at least two different agents configured to
combine upon administration of the frozen piercing implement. In
one embodiment, the at least two different agents are configured to
react upon administration of the frozen piercing implement. In one
embodiment, the at least two different agents are configured to act
cooperatively or synergistically upon administration of the frozen
piercing implement.
In one embodiment, the frozen piercing implement further comprises
at least one detection material. As described herein, in one
embodiment, the detection material includes at least one of a
contrast agent, sensor, or electronic identification device. In one
embodiment, the at least one electronic identification device
includes at least one radio frequency identification device. In one
embodiment, the detection material includes at least one of a
radioactive, luminescent, colorimetric or odorous substance. In one
embodiment, the at least one radioactive, luminescent, colorimetric
or odorous substance includes at least one temperature-sensitive
substance. In one embodiment, the detection material includes at
least one of a diamagnetic particle, ferromagnetic particle,
paramagnetic particle, super paramagnetic contrast agent, particle
with altered isotope, or other magnetic particle.
In one embodiment, the frozen piercing implement includes at least
one conduit configured to deliver at least one electrical charge,
electromagnetic energy, or other substances. In one embodiment, the
frozen piercing implement includes one or more cavities or
channels. The cavity can be in the form of a pit, pore, core,
coating, or other area of concentration.
In one embodiment, the at least one channel extends across at least
one major dimension of the at least one frozen piercing implement.
In one embodiment, the at least one channel includes at least one
of an organic or inorganic small molecule, clathrate or caged
compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, glycopeptide, glycolipid, lipoprotein,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome,
nucleus, acid, support structure, buffer, protic solvent, aprotic
solvent, nitric oxide, nitrous oxide, nitric oxide synthase, amino
acid, micelle, polymer, copolymer, monomer, prepolymer, cell
receptor, adhesion molecule, cytokine, chemokine, immunoglobulin,
antibody, antigen, platelet, extracellular matrix, blood, plasma,
cell ligand, zwitterionic material, cationic material,
oligonucleotide, nanotube, piloxymer, transfersome, gas, element,
contaminant, radioactive particle, hormone, microorganism,
bacteria, virus, quantum dot, contrast agent, or any part thereof.
In one embodiment, a method comprises sensing or extracting at
least one material from the at least one substrate. Thus, the at
least one frozen piercing implement or frozen particle composition
can include methods for chemical testing of a subject (e.g.,
pharmaceutical drugs, illicit drugs, toxins or poisons, biochemical
disorders, or dietary deficiencies, etc.).
In one embodiment, the at least one channel is configured to
deliver at least one agent or at least one detection material to
the at least one substrate. In one embodiment, the at least one
channel is configured to deliver at least one agent, or detection
material by at least one of: van der Waals forces, gravitational
force, electrostatic energy, hydration attraction, hydration
repulsion, hydrophobic attraction, hydrophobic repulsion,
diffusion, osmosis, mechanical pump, electroosmosis,
electrophoresis, convection, sublimation, hydroloysis, magnetic
attraction or repulsion, capillary action, pressure gradient,
concentration gradient, electricity, ultrasound, receptor binding,
heat, chemical, chemical reaction, tunablemicrolens or nanolens,
gate or valve, or external applied force.
In one embodiment, the external applied force includes one or more
of physical propulsion, thermal displacement, laminar flow,
turbulent flow, x-rays, gamma rays, electron beams, proton beams,
or acoustic droplet ejection. In one embodiment, the at least one
channel of the frozen piercing implement contains at least one
agent. In one embodiment, the at least one channel of the frozen
piercing implement contains at least one of an ion exchange
material, ion selective material, permeable material, solid
material, or semi-permeable material. In one embodiment, the wall
thickness of the at least one channel is approximately 1 nm,
approximately 10 nm, approximately 50 nm, approximately 100 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, or any value therebetween.
In one embodiment, at least one surface of the at least one channel
is substantially hydrophobic. In one embodiment, at least one
surface of the at least one channel is substantially
hydrophilic.
In one embodiment, the at least one frozen piercing implement
includes one or more layers. In one embodiment, the at least one
frozen piercing implement includes at least one layer of a
different constitution than at least one other layer. In one
embodiment, the frozen piercing implement approximates the shape of
at least one of a sphere, bullet, flechette, cone, frustum, needle,
arrow, spear, diamond, pyramid, cylinder, minie ball, shuttlecock,
spiral, bell, pear, crystal, cube, spheroid, tetrahedron, crescent,
possesses a high aspect ratio shape, or any combination thereof. In
one embodiment, the frozen piercing implement possesses a high
aspect ratio shape from largest to smallest dimension of greater
than or approximately equal to 1.1, greater than or approximately
equal to 1.5, greater than or approximately equal to 2.0, greater
than or approximately equal to 3.0, greater than or approximately
equal to 5.0, greater than or approximately equal to 10.0, greater
than or approximately equal to 20.0, greater than or approximately
equal to 50.0, greater than or approximately equal to 100.0,
greater than or approximately equal to 1000.0, or any value
therebetween.
In one embodiment, the at least one implement is configured to melt
or evaporate prior to, during, or subsequent to contacting the at
least one substrate. In one embodiment, the at least one implement
is configured to melt within the at least one substrate. In one
embodiment, the at least one implement is configured to be
substantially removed from the at least one substrate. In one
embodiment, the at least one implement is configured to penetrate
at least an outer surface layer of the at least one substrate.
In one embodiment, the frozen piercing implement includes at least
a portion of a piercing instrument. In one embodiment, the frozen
piercing implement includes at least approximately 5%,
approximately 10%, approximately 20%, approximately 30%,
approximately 40%, approximately 50%, approximately 60%,
approximately 70%, approximately 80%, approximately 90%,
approximately 100%, or any value less than or therebetween portion
of a piercing instrument. In one embodiment, the piercing
instrument includes at least one of metal, wood, plastic,
fiberglass, or other material. In one embodiment, the piercing
instrument includes at least one solid internal portion. In one
embodiment, the at least one solid internal portion is sterile. In
one embodiment, the implement includes at least one solid internal
portion and at least one sterile frozen hydrogen oxide external
coating. In one embodiment, the frozen external coating is
configured to melt or evaporate prior to, during, or subsequent to
piercing the at least one substrate. In one embodiment, the at
least one solid internal portion is configured to be removed from
the at least one substrate. In one embodiment, the at least one
implement is configured to break off within the at least one
substrate. In one embodiment, the at least one implement is
configured to break off due to an applied load. In one embodiment,
the at least one implement is configured to break off due to
thermal input. In one embodiment, the thermal input includes at
least one thermal input from at least one internal or external
source. In one embodiment, the at least one external source
includes the at least one substrate. In one embodiment, the at
least one implement is configured to break off due to at least one
weak portion of the implement.
In one embodiment, the frozen piercing implement further includes
at least one non-frozen implement holding device. In one
embodiment, the at least one non-frozen implement holding device
includes at least one handle, robotic arm, or surgical device. In
one embodiment, the frozen piercing implement is approximately
solid. In one embodiment, the frozen piercing implement is
approximately semi-permeable. In one embodiment, the frozen
piercing implement includes one or more pits or ports. In one
embodiment, the frozen piercing implement includes at least one
substantially tapered end. In one embodiment, the at least one
substantially tapered end includes an angle of approximately
30.degree., approximately 40.degree., approximately 50.degree.,
approximately 60.degree., approximately 70.degree., approximately
80.degree., approximately 90.degree., or any value therebetween or
greater. In one embodiment, the angle includes a wall angle.
In one embodiment, the frozen piercing implement includes at least
one substantially beveled end. In one embodiment, the at least one
substantially beveled end includes an angle of approximately
30.degree., approximately 40.degree., approximately 50.degree.,
approximately 60.degree., approximately 70.degree., approximately
80.degree., approximately 90.degree., or any value therebetween or
greater. In one embodiment, the angle includes a wall angle. In one
embodiment, the frozen piercing implement includes at least one
substantially jagged or substantially serated end. In one
embodiment, the frozen piercing implement substantially
approximates at least one projection. In one embodiment, the at
least one projection substantially terminates in at least one tip.
In one embodiment, the at least one tip is substantially hollow. In
one embodiment, a substantially jagged or serated end includes
multiple protrusions or peaks. In one embodiment, the serated or
substantially jagged end allows for increased substrate
penetration, increased substrate ablation or abrasion, increased
end surface area, or increased carrying capacity for at least one
agent. See, for example, U.S. Pat. No. 5,457,041, which is
incorporated herein by reference.
In one embodiment, the radius of the at least one tip is
approximately 1 nm, approximately 10 nm, approximately 100 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 gm, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, or any value
therebetween.
In one embodiment, the radius of curvature of the tip is
approximately 1 nm, approximately 10 nm, approximately 100 nm,
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 50 .mu.m, approximately 100 .mu.m,
approximately 500 .mu.m, approximately 1 mm, approximately 5 mm, or
any value therebetween. In one embodiment, the frozen piercing
implement includes at least one port. In one embodiment, the at
least one port includes at least one side port. In one embodiment,
the at least one port includes at least one end port. In one
embodiment, the at least one port includes at least one inlet port.
In one embodiment, the at least one inlet port is in fluid
communication with at least one channel. In one embodiment, the at
least one port includes at least one outlet port. In one
embodiment, the at least one outlet port is in fluid communication
with at least one channel. In one embodiment, the at least one port
includes at least one inlet port in fluid communication with at
least one outlet port.
In one embodiment, the frozen piercing implement is formulated to
be administered to the at least one substrate. In one embodiment,
the at least one substrate includes one or more of a cell, tissue,
organ, structure, device, or food product. In one embodiment, the
at least one substrate includes at least one food product.
In one embodiment, the frozen piercing implement is configured to
pierce at least one substrate to a depth of approximately 1 .mu.m,
approximately 5 .mu.m, approximately 10 .mu.m, approximately 15
.mu.m, approximately 20 .mu.m, approximately 50 .mu.m,
approximately 100 .mu.m, approximately 120 .mu.m, approximately 150
.mu.m, approximately 200 .mu.m, approximately 250 .mu.m,
approximately 300 .mu.m, approximately 350 .mu.m, approximately 400
.mu.m, approximately 450 .mu.m, approximately 500 .mu.m,
approximately 600 .mu.m, approximately 700 .mu.m, approximately 800
.mu.m, approximately 900 .mu.m, approximately 1 mm, approximately 2
mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, or
any value therebetween. In one embodiment, the at least one frozen
piercing implement is configured to abrade or ablate at least one
substrate surface. In one embodiment, the plurality of frozen
piercing implements is positioned such that each frozen piercing
implement of the array device contacts a single cell of at least
one biological tissue.
In one embodiment, the piercing includes abrading or ablating at
least a portion of the surface of the at least one substrate. In
one embodiment, the piercing includes abrading or ablating one or
more cells or tissues.
In one embodiment, the at least one frozen piercing implement
includes at least one sensor. In one embodiment, the at least one
sensor includes at least one sensor configured for detecting at
least one of a biochemical, electrical, optical, functional,
physical, chemical, biological, or structural characteristic of the
at least one material. In one embodiment, the at least one frozen
piercing implement is configured for extracting at least one
material from the at least one substrate. In one embodiment, the at
least one material includes one or more of a cell, organic or
inorganic small molecule, vesicle, micelle, organelle, cell
membrane, nucleic acid, peptide, polypeptide, protein,
oligosaccharide, polysaccharide, glycopeptide, glycolipid,
lipoprotein, sphingolipid, glycosphingolipid, glycoprotein,
peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan,
chromosome, cell nucleus, amino acid, polymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
transfersome, gas, element, contaminant, radioactive particle,
hormone, or any part thereof.
In one embodiment, the at least one frozen piercing implement is
configured for extracting at least one material from the at least
one substrate by at least one of: van der Waals forces,
gravitational pull, electrostatic energy, hydration attraction,
hydration repulsion, hydrophobic attraction, hydrophobic repulsion,
magnetic attraction, magnetic repulsion, capillary action, or
external applied force. In one embodiment, the frozen piercing
implement further comprises at least one of an organic or inorganic
small molecule, clathrate or caged compound, protocell, coacervate,
microsphere, Janus particle, proteinoid, laminate, helical rod,
liposome, macroscopic tube, niosome, sphingosome, toroid, vesicular
tube, vesicle, small unilamellar vesicle, large unilamellar
vesicle, large multilamellar vesicle, multivesicular vesicle, lipid
layer, lipid bilayer, micelle, organelle, cell, membrane, nucleic
acid, peptide, polypeptide, protein, glycopeptide, glycolipid,
lipoprotein, sphingolipid, glycosphingolipid, glycoprotein,
peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan,
chromosome, nucleus, acid, support structure, buffer, protic
solvent, aprotic solvent, nitric oxide, nitrous oxide, nitric oxide
synthase, amino acid, micelle, polymer, copolymer, monomer,
prepolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, piloxymer, transfersome, gas,
element, contaminant, radioactive particle, hormone, microorganism,
bacteria, virus, quantum dot, contrast agent, or any part
thereof.
In one embodiment, the frozen piercing implement includes one or
more of nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment, a plurality of frozen piercing implements is
disclosed. In one embodiment, the frozen piercing implement is
included in at least one frozen piercing implement device. In one
embodiment, the at least one frozen piercing implement device
includes at least one of a frozen piercing implement array device,
frozen piercing implement fluidic device, or frozen piercing
implement injection device. In one embodiment, the frozen piercing
implement device includes at least one of a patch, bandage, shunt,
wound dressing, splint, computer mouse, telephone, mobile phone,
writing instrument, article of clothing, blanket, pen-type device,
other article of manufacture, or medical instrument. In one
embodiment, the frozen piercing implement device includes at least
one cooling element. In one embodiment, the at least one cooling
element includes one or more of a refrigeration mechanism, heat
exchanger, thermoelectric, cold plate, low temperature thermal
ballast, or phase change material.
In one embodiment, the frozen piercing implement includes one or
more of a suspension, mixture, solution, sol, clathrate, colloid,
emulsion, microemulsion, aerosol, ointment, capsule, powder,
tablet, suppository, cream, device, paste, resin, liniment, lotion,
ampule, elixir, spray, syrup, tincture, detection material,
polymer, biopolymer, buffer, adjuvant, diluent, lubricant,
disintegration agent, suspending agent, solvent, light-emitting
agent, colorimetric agent, glidant, anti-adherent, anti-static
agent, surfactant, plasticizer, emulsifying agent, flavor, gum,
sweetener, coating, binder, filler, compression aid, encapsulation
aid, preservative, granulation agent, spheronization agent,
stabilizer, adhesive, pigment, sorbent, nanoparticle, or gel. In
one embodiment, the frozen piercing implement further comprises at
least one pharmaceutically-acceptable carrier or excipient.
In one embodiment, the frozen piercing implement is substantially
in the form of at least one blade. In one embodiment, the at least
one blade is at least part of one or more of a knife, razor,
scissors, hatchet, saw, rotary device, or scalpel. In one
embodiment, the at least one frozen piercing implement is
configured as a tweezers, fork, scriber, graver, spade, screw,
needle or pin. In one embodiment, the needle or pin include at
least one macroneedle, macropin, microneedle, micropin, nanoneedle,
or nanopin. In one embodiment, the frozen piercing implement is
formulated to be administered by one or more of topical
administration, oral administration, enteral administration,
mucosal administration, percutaneous administration, or parenteral
administration. In one embodiment, the frozen piercing implement is
formulated to be administered by high velocity impact. In one
embodiment, the frozen piercing implement is formulated to be
administered by one or more devices.
In certain instances, the frozen piecing implement is utilized in
compositions or methods for delivery of at least one agent,
including but not limited to a therapeutic agent, adhesive agent,
reinforcement agent, biological remodeling agent, explosive
material, or abrasive.
In one embodiment, the frozen piercing implementation is utilized
in compositions or methods for transdermal therapeutic agent
delivery, including but not limited to vaccine delivery.
In one embodiment, the frozen piercing implements or tools are
utilized in compositions or methods for electrotherapy, nucleic
acid sampling, protein sampling, cell sampling, tissue sampling,
nucleic acid analysis, protein analysis, cell analysis, tissue
analysis, iontophoresis, or other technique. In one embodiment, the
at least one frozen piercing implement includes at least one of a
channel, pump, sensor, injector, actuator, heater, detector,
controller, transducer, receiver, transmitter, circuit, lens,
tunable lens, valve, gate, nanoparticle, microparticle, power
source, or detection material. In one embodiment, the frozen
piercing implement includes at least one waveguide that provides a
path to guide energy waves.
In one embodiment, the frozen piercing implement includes a length
of approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, approximately 10 mm,
approximately 20 mm, approximately 30 mm, approximately 40 mm,
approximately 50 mm, approximately 60 mm, approximately 70 mm,
approximately 80 mm, approximately 90 mm, approximately 100 mm,
approximately 200 mm, approximately 300 mm, approximately 400 mm,
approximately 500 mm, approximately 600 mm, approximately 700 mm,
approximately 800 mm, approximately 900 mm, approximately 1 cm,
approximately 10 cm, approximately 20 cm, or any value
therebetween.
In one embodiment, the frozen piercing implement has a
substantially solid form. In one embodiment, the frozen piercing
implement has a substantially semi-permeable form. In one
embodiment, the frozen piercing implement includes at least one
channel, providing the frozen piercing implement with at least one
inner diameter and at least one outer diameter.
In one embodiment, the frozen piercing implement includes an outer
diameter of approximately 1 nm, approximately 10 nm, approximately
100 nm, approximately 1 .mu.m, approximately 5 .mu.m, approximately
10 .mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, approximately 10 mm,
approximately 20 mm, approximately 30 mm, approximately 40 mm,
approximately 50 mm, approximately 60 mm, approximately 70 mm,
approximately 80 mm, approximately 90 mm, approximately 100 mm,
approximately 200 mm, approximately 300 mm, approximately 400 mm,
approximately 500 mm, approximately 600 mm, approximately 700 mm,
approximately 800 mm, approximately 900 mm, approximately 1 cm,
approximately 10 cm, or any value therebetween.
In one embodiment, the frozen piercing implement has an inner
diameter, and includes an inner diameter of approximately 1 nm,
approximately 10 nm, approximately 100 nm, approximately 1 .mu.m,
approximately 5 .mu.m, approximately 10 .mu.m, approximately 15
.mu.m, approximately 20 .mu.m, approximately 50 .mu.m,
approximately 100 .mu.m, approximately 120 .mu.m, approximately 150
.mu.m, approximately 200 .mu.m, approximately 250 .mu.m,
approximately 300 .mu.m, approximately 350 .mu.m, approximately 400
.mu.m, approximately 450 .mu.m, approximately 500 .mu.m,
approximately 600 .mu.m, approximately 700 .mu.m, approximately 800
.mu.m, approximately 900 .mu.m, approximately 1 mm, approximately 2
mm, approximately 3 mm, approximately 4 mm, approximately 5 mm,
approximately 10 mm, approximately 20 mm, approximately 30 mm,
approximately 40 mm, approximately 50 mm, approximately 60 mm,
approximately 70 mm, approximately 80 mm, approximately 90 mm,
approximately 100 mm, approximately 200 mm, approximately 300 mm,
approximately 400 mm, approximately 500 mm, approximately 600 mm,
approximately 700 mm, approximately 800 mm, approximately 900 mm,
approximately 1 cm, approximately 10 cm, or any value
therebetween.
In one embodiment, a single frozen piercing implement pierces a
single cell. In one embodiment, a single frozen piercing implement
pierces multiple cells. In one embodiment, a single frozen piercing
implement pierces at least one biological tissue. Most cells in an
animal, such as a human, are approximately 10-30 .mu.m in diameter,
while most plant and fungal cells are approximately 10-100 .mu.m in
diameter. Thus, in one embodiment, at least one of the inner or
outer diameter is configured in size according to the targeted
cell(s).
In one embodiment, the pressure exerted on a substrate is adjusted
for use of one or more frozen piercing implements. In one
embodiment, the pressure exerted on a substrate is increased or
decreased in order to adjust the rate of melting, sublimation,
evaporation, transformation, activation, etc. of the one or more
frozen piercing implements or a component thereof.
In one embodiment, the frozen piercing implement is configured to
pierce or penetrate at least one substrate. In at least one
embodiment, at least a portion of the at least one substrate
includes skin or surface of a tissue, organ, or subject's body. In
one embodiment, the frozen piercing implement is configured to
pierce or penetrate at least a portion of the stratum corneum,
epidermis, or dermis layer of the skin. In one embodiment, the
frozen piercing implement is administered prior to, during, or
subsequent to surgery.
In one embodiment, the at least one frozen piercing implement is
configured to substantially form at least one blade. In one
embodiment, the at least one blade is at least part of one or more
of a knife, razor, scissors, hatchet, saw, rotary device, or
scalpel. In one embodiment, the at least one frozen piercing
implement is configured as a tweezers, fork, scriber, graver,
spade, needle or pin. In one embodiment, the needle or pin include
at least one macroneedle, macropin, microneedle, micropin,
nanoneedle, or nanopin.
The epidermis layer of the skin is approximately 100-150 .mu.m
thick, and includes an outermost layer, the stratum corneum, which
is approximately 10-15 .mu.m in thickness. In certain areas, the
blood vessels are generally present more superficially than nerves,
which allows for delivery of at least one agent, or extraction of
at least one material from the skin and underlying tissue, largely
without activating the nerves and signaling pain. See, e.g., Kumar
and Philip, Trop. J. Pharm Res. 6(1):633-644 (2007), which is
incorporated herein by reference. In certain instances, it is
desirable to penetrate the epidermis and/or dermis layer of the
skin in order to deliver at least one agent (including but not
limited to a therapeutic agent) to a subcutaneous, intravenous, or
other location beneath the skin. In one embodiment, the frozen
piercing implement is configured to deliver at least one agent
beneath the surface of the skin or outer covering of the tissue,
organ, or subject's body. In one embodiment, the frozen piercing
implement is configured to pierce or penetrate the skin largely
without activating nerves beneath the skin.
In one embodiment, the frozen piercing implement includes at least
one functionalized surface. In one embodiment, the functionalized
surface includes one or more functional groups including but not
limited to at least one of a binding group (e.g., coupling agents,
and the like), a linking group (e.g., spacer groups, organic spacer
groups, and the like), or a matrix-forming group. Some examples of
binding groups include but are not limited to at least one
acrylate, alkoxysilane, alkyl thiol, arene, azido, carboxylate,
chlorosilane, alkoxysilane, acetocysilane, silazane, disilazane,
disulfide, epoxide, ester, hydrosilyl, isocyanate, phosphoamidite,
isonitrile, methacrylate, nitrene, nitrile, quinone, silane,
sulfhydryl, thiol, vinyl group, and the like. Some examples of
linking groups include but are not limited to at least on
dendrimer, polymer, hydrophilic polymer, hyperbranched polymer,
poly(amino acid), polyacrylamide, polyacrylate, polyethylene
glycol, polyethylenimine, polymethacrylate, polyphosphazene,
carbohydrate, monosaccharide, disaccharide, polysaccharide,
polysiloxane, polystyrene, polyurethane, propylene, amino acid,
nucleic acid, polypeptide, protein, copolymer, block copolymer, and
the like. Some examples of matrix-forming groups include but are
not limited to at least one dendrimer polyamine polymer, bovine
serum albumin, casein, glycolipid, lipid, heparin,
glycosaminoglycan, mucin, surfactant, polyoxyethylene-based
surface-active substance (e.g., polyoxyethlene-polyoxypropylene
copolymer, polyoxyethylene 12 tridecyl ether, polyoxyethylene 18
tridecyl ether, polyoxyethylene 6 tridecyl ether, polyoxyethylene
sorbitan tetraoleate, polyoxyethylene sorbitol hexaoleate, and the
like) polyethylene glycol, saccharide, polysaccharide, serum
dilution, and the like.
In one embodiment, the one or more functional groups include
charged functional groups capable of maintaining a positive or
negative charge over a wide range of pH. Some examples of charged
functional groups include but are not limited to at least one
cation, anion, amine, acid, halocarbon, sulfonic acid, quaternary
amine, metal, --NH.sub.3.sup.+, --COOH, --COO--, --SO.sub.3,
CH.sub.2N.sup.+(CH.sub.3).sub.3, and the like.
In one embodiment, the one or more frozen piercing implements are
tested for constitution, physical structure, physical integrity, or
other property. In one embodiment, the one or more frozen piercing
implements are designed with assistance from at least one computer
program or computing device.
In one embodiment, a method of administering at least one frozen
piercing implement to at least one substrate comprises contacting
at least one frozen piercing implement with at least one substrate,
wherein the at least one frozen piercing implement includes sterile
frozen hydrogen oxide and at least one agent; and wherein the
frozen piercing implement has at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween.
In one embodiment, wherein administering the at least one frozen
piercing implement to at least one substrate includes propelling,
ejecting, or accelerating the at least one frozen piercing
implement toward the at least one substrate at a predetermined
angle, a predetermined velocity, a predetermined rate of
administration, a predetermined depth, a predetermined location, a
predetermined time sequence, or a predetermined spatial pattern. In
one embodiment, the method further comprises varying the rate,
velocity, or angle at which the at least one frozen piercing
implement is administered to the at least one substrate. In one
embodiment, the method includes administering the at least one
frozen piercing implement to at least one substrate by propelling,
ejecting, or accelerating a plurality of frozen piercing implements
toward the at least one substrate.
In one embodiment, the frozen piercing implement is configured to
pierce or penetrate at least one substrate. Certain examples of
substrates are provided herein. In one embodiment, the temperature
of the substrate is adjusted prior to, during, or subsequent to
administration of one or more frozen piercing implements. In one
embodiment, the temperature of the substrate is increased or
decreased in order to adjust the rate, for example, of melting,
sublimation, evaporation, transformation, activation, etc. of the
one or more frozen piercing implements or a component thereof. In
one embodiment, the method further comprises adjusting the
temperature of the at least one substrate prior to, during, or
subsequent to administering the one or more frozen piercing
implements to at least approximately 37.degree. C., approximately
36.degree. C., approximately 35.degree. C., approximately
34.degree. C., approximately 33.degree. C., approximately
32.degree. C., approximately 31.degree. C., approximately
30.degree. C., approximately 29.degree. C., approximately
28.degree. C., approximately 27.degree. C., approximately
26.degree. C., approximately 25.degree. C., approximately
24.degree. C., approximately 23.degree. C., approximately
22.degree. C., approximately 21.degree. C., approximately
20.degree. C., approximately 19.degree. C., approximately
18.degree. C., approximately 17.degree. C., approximately
16.degree. C., approximately 15.degree. C., approximately
14.degree. C., approximately 13.degree. C., approximately
12.degree. C., approximately 11.degree. C., approximately
10.degree. C., approximately 9.degree. C., approximately 8.degree.
C., approximately 7.degree. C., approximately 6.degree. C.,
approximately 5.degree. C., approximately 4.degree. C.,
approximately 3.degree. C., approximately 2.degree. C.,
approximately 1.degree. C., approximately 0.degree. C., or any
temperature therebetween.
In one embodiment, contacting at least one substrate includes at
least one of cutting, stitching, cauterizing, freezing,
perforating, penetrating, ablating, or abrading at least a part of
the surface of the at least one substrate. In one embodiment,
administering the at least one substrate occurs in conjunction with
cryosurgery, cryotherapy, or mesotherapy.
In one embodiment, contacting at least one substrate affects one or
more of electrical resistance of the at least one substrate, or
permeability of the at least one substrate. In one embodiment, at
least one frozen piercing implement is administered to at least one
substrate as party of a method for vaccination. In one embodiment,
a method of vaccinating a subject comprises administering at least
one frozen piercing implement or frozen particle composition
described herein.
Frozen Piercing Implement Devices
In one embodiment, at least one frozen piercing implement or frozen
particle composition (including a therapeutic composition) is
utilized to fabricate at least one device. In one embodiment, the
frozen piercing implement device includes at least one array
device, fluidic device, or injection device. In one embodiment, the
frozen piercing implement device includes at least one of a patch,
bandage, shunt, wound dressing, splint, computer mouse, telephone,
mobile phone, writing instrument, article of clothing, blanket,
pen-type device, other article of manufacture, or medical
instrument.
In one embodiment, a fluidic device, comprises: a support structure
at least partially defining at least one compartment; and at least
one frozen piercing implement in fluid communication with the at
least one compartment; wherein the at least one frozen piercing
implement has at least one major dimension of approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer
or less, or any value therebetween.
In one embodiment, an array device, comprises: a support structure
having a surface; and a plurality of sterile frozen piercing
implements extending substantially outward from the support
structure. In one embodiment, the plurality of sterile frozen
piercing implements having at least one major dimension of
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween.
In one embodiment, an array device comprises: a support structure
having a surface; a plurality of piercing implements extending
substantially outward from the surface of the support structure;
wherein at least one piercing implement of the plurality of
piercing implements includes a frozen piercing implement. In one
embodiment, the at least one frozen piercing implement has at least
one major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer or less, or any value
therebetween.
In one embodiment, a composition, comprises: a plurality of
piercing implement array devices joined together, the piercing
implement array devices including at least one frozen piercing
implement.
In one embodiment, a composition, comprises: a support means for an
array device; wherein the array device includes one or more frozen
piercing implements.
In one embodiment, the plurality of sterile frozen piercing
implements have at least one major dimension of approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween. In one embodiment, the plurality of
sterile frozen piercing implements extends substantially
perpendicular to the support structure. In certain instances, the
frozen piercing implements extend through the support structure, or
from the surface of the support structure. In one embodiment, the
support structure itself includes at least one frozen composition.
In one embodiment, the support structure includes at least one
frozen composition also included in at least one frozen piercing
implement. In one embodiment, the support structure is at least
partially frozen. In one embodiment, the support structure and at
least one frozen piercing implement of the plurality of frozen
piercing implements include at least one common constituent.
In one embodiment, the plurality of frozen piercing implements are
positioned substantially parallel to each other. In one embodiment,
the plurality of frozen piercing implements are positioned
substantially in a predetermined spatial pattern. In one
embodiment, the predetermined spatial pattern is at least partially
periodic. In one embodiment, the plurality of frozen piercing
implements includes an area density of implements greater than or
approximately equal to 1 .mu.m, greater than or approximately equal
to 10 .mu.m, greater than or approximately equal to 50 .mu.m,
greater than or approximately equal to 100 .mu.m, greater than or
approximately equal to 500 .mu.m, greater than or approximately
equal to 1 mm, greater than or approximately equal to 10 mm,
greater than or approximately equal to 50 mm, greater than or
approximately equal to 100 mm, greater than or approximately equal
to 500 mm, greater than or approximately equal to 1 cm, or any
value there between. In one embodiment, the plurality of frozen
piercing implements include approximately the same length.
In one embodiment, the length of a frozen piercing implement is
associated with the position or location of the frozen piercing
implement in the array device. In one embodiment, the length of a
frozen piercing implement is actuatable. In one embodiment, at
least one frozen piercing implement is configured to be
deactivated. In one embodiment, the at least one frozen piercing
implement configured to be deactivated is deactivated by at least
one component of the array device or the frozen piercing implement.
In one embodiment, the at least one frozen piercing implement
configured to be deactivated is deactivated by thermal transfer to
the at least one frozen piercing implement.
In one embodiment, the plurality of frozen piercing implements is
positioned as at least a portion of a fluidic or injection device.
In one embodiment, the plurality of frozen piercing implements is
positioned in fluid communication with at least one compartment
configured to be mechanically regulated. In one embodiment, at
least one frozen piercing implement of the plurality of frozen
piercing implements includes one or more of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment, at least one frozen piercing implement of the
plurality of frozen piercing implements is configured to deliver at
least one agent. In one embodiment, the at least one major
dimension includes at least one of the radius, diameter, length,
width, height, or perimeter. In one embodiment, at least one frozen
piercing implement of the plurality further comprises at least one
agent. In one embodiment, each frozen piercing implement of the
plurality includes at least one agent different than the agent of
every other frozen piercing implement of the plurality. In one
embodiment, at least one frozen piercing implement of the plurality
includes at least two different agents. In one embodiment, the
device includes at least two different agents. In one embodiment,
the at least one agent includes at least one antigen. In one
embodiment, each frozen piercing implement of the plurality
includes at least one antigen. In one embodiment, the at least one
antigen includes at least one allergen. In one embodiment, the
frozen piercing implement is configured for delivering the at least
one agent. In one embodiment, the at least one agent includes at
least one of a nontoxic, biocompatible, bioresorbable, or
biodegradable agent.
In one embodiment, at least two frozen piercing implements of the
plurality of frozen piercing implements have at least one agent in
common. In one embodiment, each frozen piercing implement of the
plurality of frozen piercing implements has at least one agent in
common. In one embodiment, each frozen piercing implement of the
plurality of frozen piercing implement is different from every
other piercing implement by varying one or more of: size of
implement, shape of implement, or constitution of implement. In one
embodiment, at least two frozen piercing implements of the
plurality of frozen piercing implement differ in one or more of:
size of implement, shape of implement, or constitution of
implement.
As described herein, in one embodiment, at least one of the
plurality of frozen peiercing implements is substantially solid at
approximately 0.degree. C., approximately -10.degree. C.,
approximately -20.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -75.degree. C., approximately -80.degree. C.,
approximately -85.degree. C., approximately -90.degree. C.,
approximately -95.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -180.degree. C., approximately -200.degree. C.,
approximately -220.degree. C., approximately -250.degree. C., or
any value less than or therebetween. Ranges for consideration of
substantially solid state are provided herein.
In one embodiment, the array device has at least one major
dimension of approximately one centimeter or less, approximately
one millimeter or less, approximately one micrometer or less,
approximately one nanometer, or any value therebetween. In one
embodiment, the plurality of frozen piercing implements includes a
two dimensional array. In one embodiment, the plurality of frozen
piercing implements includes a three dimensional array. In one
embodiment, the plurality of frozen piercing implements are
arranged in at least one configuration including a regular or
irregular shape. In one embodiment, the plurality of frozen
piercing implements are arranged in at least one configuration
including at least one of a rectangle, square, circle, triangle, or
polygon.
In one embodiment, at least one frozen piercing implement of the
plurality of frozen piercing implements includes at least one
functionalized surface. In one embodiment, the at least one
functionalized surface includes one or more functionalities
including one or more of charge functionality, hydrophobic
functionality, hydrophilic functionality, chemically reactive
functionality, organo functionality, or wetability. In one
embodiment, the at least one functionalized surface includes one or
more functional groups including at least one of an agent, alcohol,
hydroxyl, amine, aldehyde, dye, ketone, carbonyl, thiol,
alkoxysilane, phosphate, carboxyl, carboxylic acid, carboxylate,
nucleic acid, amino acid, polypeptide, protein, lipid,
carbohydrate, metal, --NH.sub.3.sup.+, --COOH, --COO--, --SO.sub.3,
CH.sub.2N.sup.+(CH.sub.3).sub.3, --(CH.sub.2).sub.xCH.sub.3,
--C((CH.sub.2).sub.xCF.sub.3).sub.3,
--CH.sub.2N(C.sub.2H.sub.5).sub.2, --NH.sub.2,
--(CH.sub.2).sub.xCOOH, --(OCH.sub.2CH.sub.2).sub.xCH.sub.3,
--SiOH, or --OH. In one embodiment, the at least one functionalized
surface includes at least part of an outer surface. In one
embodiment, the at least one functionalized surface includes at
least part of an inner surface.
In one embodiment, the array device further comprises at least one
channel. In one embodiment, the at least one channel includes at
least one cross-coupling flow channel. In one embodiment, at least
one frozen piercing implement of the plurality of frozen piercing
implements includes at least one inlet port. In one embodiment, the
at least one inlet port is in fluid communication with at least one
channel of at least one frozen piercing implement. In one
embodiment, the at least one inlet port is in fluid communication
with at least one channel of the array device. In one embodiment,
at least one frozen piercing implement of the plurality of frozen
piercing implements includes a plurality of inlet ports. In one
embodiment, at least one frozen piercing implement of the plurality
of frozen piercing implements includes at least one outlet port. In
one embodiment, the at least one outlet port is in fluid
communication with at least one channel of at least one frozen
piercing implement. In one embodiment, the at least one outlet port
is in fluid communication with at least one channel of the array
device. In one embodiment, at least one frozen piercing implement
of the plurality of frozen piercing implements includes a plurality
of outlet ports. In one embodiment, the array device further
comprises at least one of a nanoparticle, microparticle, sensor,
valve, gate, channel, transducer, actuator, detector, heater,
circuit, or detection material.
In one embodiment, at least one implement of the plurality of
frozen piercing implements includes at least one sensor. In one
embodiment, at least one implement of the plurality of frozen
piercing implements is configured for extracting at least one
material from at least one substrate. Various non-limiting examples
of materials capable of being sensed, extracted, or collected from
a substrate are provided herein.
In one embodiment, at least one implement of the plurality of
frozen piercing implements further includes at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof.
In one embodiment, the plurality of frozen piercing implements
includes at least approximately 2 implements, approximately 5
implements, approximately 10 implements, approximately 20
implements, approximately 50 implements, approximately 100
implements, approximately 200 implements, approximately 300
implements, approximately 400 implements, approximately 500
implements, approximately 600 implements, approximately 700
implements, approximately 800 implements, approximately 900
implements, approximately 1000 implements, approximately 5000
implements, approximately 10000 implements, or any value
therebetween or greater. In one embodiment, the spacing between two
or more frozen piercing implements includes at least approximately
1 nm, approximately 5 nm, approximately 10 nm, approximately 20 nm,
approximately 50 nm, approximately 80 nm, approximately 100 nm,
approximately 200 nm, approximately 300 nm, approximately 400 nm,
approximately 500 nm, approximately 600 nm, approximately 700 nm,
approximately 800 nm, approximately 900 nm, approximately 1 .mu.m,
approximately 5 .mu.m, approximately 10 .mu.m, approximately 15
.mu.m, approximately 20 .mu.m, approximately 50 .mu.m,
approximately 100 .mu.m, approximately 120 .mu.m, approximately 150
.mu.m, approximately 200 .mu.m, approximately 500 .mu.m,
approximately 1 mm, approximately 5 mm, approximately 10 mm,
approximately 100 mm, approximately 500 mm, approximately 1 cm,
approximately 5 cm, approximately 10 cm, or any value therebetween
or greater. In one embodiment, the array device further comprises
at least one attachment component configured to secure the array
device to at least one substrate. In one embodiment, the at least
one attachment component includes at least one adhesive material.
In one embodiment, the device is configured to substantially form a
patch.
In one embodiment, the array device further comprises at least one
compartment. In one embodiment, at least one compartment includes
at least one syringe or at least one valve. In one embodiment, at
least one compartment is configured to hold at least one material
extracted from at least one substrate. In one embodiment, at least
one agent includes at least one of an adhesive agent, therapeutic
agent, reinforcement agent, abrasive, biological remodeling agent,
or explosive material.
In one embodiment, the array device further comprises at least one
compartment in fluid communication with at least one frozen
piercing implement of the plurality of frozen piercing implements.
In one embodiment, the at least one compartment is configured for
holding at least one agent. In one embodiment, the at least one
compartment is configured for holding at least one cryogenic
substance. In one embodiment, the array device further comprises a
plurality of compartments in fluid communication with at least one
frozen piercing implement of the plurality of frozen piercing
implements. In one embodiment, the plurality of compartments
includes at least one first compartment configured to hold at least
one different substance from at least one second compartment. In
one embodiment, the plurality of compartments includes at least one
first compartment configured to hold at least one first agent,
wherein the at least one first agent is different from at least one
other agent located in at least one second compartment. In one
embodiment, the plurality of compartments includes at least one
first compartment configured to hold at least one first agent, and
at least one second compartment configured to hold a
pharmaceutically acceptable carrier or excipient. In one
embodiment, two or more compartments are configured to interact
with at least one means for intermixing the contents of the two or
more compartments prior to or during administration of the array
device to at least one substrate. In one embodiment, wherein the at
least one means for intermixing includes mechanical disruption of
at least one compartment, altering porosity of at least one
compartment, electrochemical degradation of at least one
compartment, valve opening of at least one compartment, chemical
degradation of at least one compartment, or altering magnetic field
of at least one compartment. In one embodiment, the array device is
in electronic communication with at least one computing device.
In one embodiment, a composition comprises a plurality of frozen
piercing implement array devices joined together.
In one embodiment, the at least one support structure for an array
device, fluidic device, or injection device includes at least one
of a nanoparticle, sensor, circuit, lens, heater, detector,
controller, or actuator. In one embodiment, the support structure
includes at least one wave guide.
In one embodiment, the heater includes a microheater or nanoheater.
In one embodiment, the detector includes a microdetector or
nanodetector. In one embodiment, the actuator includes a
microactuator or a nanoactuator. In one embodiment, the actuator
includes a rotational actuator including carbon nanotubes. See, for
example, Fennimore et al., Nature (Abstract) vol. 424, pp. 408-410
(2003), which is incorporated herein by reference. In one
embodiment, the actuator includes a biological molecular motor or
switch (e.g., kinesin, myosin, ATP synthase, etc.). See, for
example, Dessinges et al., PNAS vol. 101, no. 17, pp. 6439-6444
(2004); which is incorporated herein by reference.
In one embodiment, the lens includes a liquid micro-lens array
activated by selective electrowetting on polar electric crystals,
including but not limited to litium niobate. See, for example,
Grilli et al., Optics Express, vol. 16, no. 11, (2008), which is
incorporated herein by reference.
In one embodiment, the frozen piercing implement, or frozen
piercing implement device, is configured to pierce at least one
substrate in a substantially painless manner. In one embodiment,
the frozen piercing implement, or frozen piercing implement device,
is configured to pierce one or more biological cells or tissues of
a subject in a substantially painless manner.
In one embodiment, the frozen piercing implement, or frozen
piercing implement device, is utilized in conjunction with at least
one other substrate-piercing tool, including but not limited to
transdermal agent delivery iontophoresis, ultrasound, vacuum,
viruses, pH, heat, light, chemical enhancers, electric fields,
photomechanical waves, mesotherapy, electroporation, electrofusion,
electroosmosis, velocity based enhancement techniques (such as
needle-free injections), tape stripping, powderjecting,
transfersomes, agent-embedded tattoos or other etchings, abrasion
or ablation, controlled heat aided delivery, laser radiation,
magnetophoresis, or others. See, for example, Kumar and Philip,
Trop. J. Pharm. Res. 6(1):633-644 (2007), which is incorporated
herein by reference. In one embodiment, the frozen piercing
implement or frozen particle composition includes at least one
general anesthetic. In one embodiment, the frozen piercing
implement or frozen particle composition including a general
anesthetic is configured to be used as at least part of a defense
weapon.
In one embodiment, the frozen piercing implement includes at least
one projection. In one embodiment, the frozen piercing implement is
configured to pierce at least one substrate to a depth of
approximately 1 .mu.m, approximately 5 .mu.m, approximately 10
.mu.m, approximately 15 .mu.m, approximately 20 .mu.m,
approximately 50 .mu.m, approximately 100 .mu.m, approximately 120
.mu.m, approximately 150 .mu.m, approximately 200 .mu.m,
approximately 250 .mu.m, approximately 300 .mu.m, approximately 350
.mu.m, approximately 400 .mu.m, approximately 450 .mu.m,
approximately 500 .mu.m, approximately 600 .mu.m, approximately 700
.mu.m, approximately 800 .mu.m, approximately 900 .mu.m,
approximately 1 mm, approximately 2 mm, approximately 3 mm,
approximately 4 mm, approximately 5 mm, approximately 10 mm,
approximately 20 mm, approximately 30 mm, approximately 40 mm,
approximately 50 mm, approximately 60 mm, approximately 70 mm,
approximately 80 mm, approximately 90 mm, approximately 100 mm,
approximately 200 mm, approximately 300 mm, approximately 400 mm,
approximately 500 mm, approximately 600 mm, approximately 700 mm,
approximately 800 mm, approximately 900 mm, approximately 1 cm,
approximately 10 cm, approximately 20 cm, or any value
therebetween.
In one embodiment, the frozen particle implement administration
depth is controlled by mechanical means. For example, the implement
administration depth may be limited by a sheath or casing. In one
embodiment, the frozen particle implement depth is controlled by a
positioner on the array that can control the depth of
administration. In one embodiment, the positioner is configured to
mechanically control the depth of administration of at least one
frozen piercing implement (or other implement if located in an
array device). Other factors that can influence administration
depth include the geometry of the implement, constitution of the
implement, administration time, manner of administration, or at
least one parameter of the substrate (including, but not limited to
temperature, constitution, density, location, etc.)
In one embodiment, one or more frozen piercing implement array
device includes at least two frozen piercing implements positioned
on or through the surface of at least one base or support
structure. In one embodiment, a flange or other member is
configured on the array device to provide physical support to the
device, to provide stabilization when the device is placed on the
substrate, or to control penetration of the substrate by the at
least one piercing implement.
In one embodiment, the frozen piercing implement array device is an
in-plane array device. In one embodiment, the frozen piercing
implement array device is an out-of-plane array device.
In one embodiment, the device includes a particular arrangement of
the piercing implements on the base or support structure (e.g.,
square, hexagonal, triangular, diamond, rectangular, or other
patterning), varying the distribution of the piercing implements
within a specific patterned or designed array device, varying at
least one dimension of the piercing implement (e.g., number of
piercing implements, piercing implement radius, etc.), number of
solid versus channeled piercing implements, among other features,
can affect the functionality of the array device. See, for example,
Al-Qallaf and Bhusan Das, J Drug Target., vol. 17, no. 2, pp.
108-122 (2009), which is incorporated herein by reference.
Furthermore, optimization of the surface area of the array device,
optimization of the piercing implement radius and length,
optimization of the number of piercing implements per row,
optimization of the aspect ratio of the distance between piercing
implements, while considering the substrate thickness or
permeability, can be conducted according to well-established
principles. Id. For example, the following equation has been used
in published studies to calculate skin permeability when using
microneedles: K=f(D/Lh), where K is the approximate skin
permeability of the agent (or other agent) intended to be
administered, f is the approximate fractional skin area after
insertion by the microneedles, D is the approximate effective
diffusion coefficient of the therapeutic agent in the skin, and
L.sub.h is the approximate length of the hole resulting from the
piercing of the skin. Id. In one embodiment, the therapeutic agent
molecules may traverse through various disruptions in the skin
thickness (i.e., epidermis) from the frozen piercing implement of
the array device to the blood supply. In one embodiment, the agent
may be absorbed as the frozen piercing implement melts or
sublimates. In one embodiment, particularly with channeled, or
hollowed, microneedles, the therapeutic agent may move through the
bore of the implement. In one embodiment, the path of the
therapeutic agent represents the approximate length of the
microneedle. In one embodiment, the path of the therapeutic agent
may be less than or greater than the approximate length of the
microneedle due to expansion or contraction of the microneedle upon
contact or penetration of the substrate.
In one embodiment, the array device is administered to at least one
external surface of a subject. In one embodiment, the array device
is administered to at least one internal surface of a subject (for
example, by utilizing a catheter, laparascope, or other tool). In
one embodiment, the array device is surgically implanted into a
subject.
In one embodiment, the one or more frozen piercing implements are
combined with at least one syringe. In one embodiment, the syringe
includes a micro- or nano-syringe. In one embodiment, the one or
more frozen piercing implements are combined with at least one
pen-type delivery device. For example, the pen-type delivery device
includes a housing assembly, a hub assembly, a plunger for driving
the piercing implement out of the housing assembly and into the
substrate, an optional compartment containing a desired substance
to be administered, and an optional mechanism for piercing the
compartment and releasing the substance. See, for example, U.S.
Patent App. Pub. No. 20030050602, which is incorporated herein by
reference.
In one embodiment, one or more frozen piercing implements are
combined with a fluidic system. In one embodiment, the fluidic
system includes a microfluidic system. In one embodiment, the
fluidic system includes a nanofluidic system. In one embodiment,
the fluidic system includes at least one of a a channel, pump,
sensor, injector, actuator, heater, detector, controller,
transducer, receiver, transmitter, circuit, lens, tunable lens,
valve, gate, nanoparticle, microparticle, power source, or
detection material.
In one embodiment, the valve includes a valve actuated by a motor.
In one embodiment, the valve includes a slide-valve, optionally
actuated by a motor. As described herein, in one embodiment, the
motor includes a biological based motor (e.g. kinesin, myosin, ATP
synthase), or a micro- or nano-stepping motor. See, for example,
Morishima et al, 7.sup.th Int. Conf. Miniaturized Chem. and
Biochem. Anal. Sys. pp. 1033-1036 (Oct. 5-9, 2003), which is
incorporated herein by reference.
In one embodiment, the fluidic device includes a closed loop system
capable of delivering at least one agent, sensing, or extracting at
least one material from at least one substrate. In one embodiment,
the fluidic system includes at least one compartment. In one
embodiment, the fluidic system senses or analyzes at least one
material from at least one substrate. In one embodiment, the
analysis includes sensing an enzyme or enzymatic reaction
including, but not limited to glucose oxidase or glucose
dehydrogenase. In one embodiment, the fluidic device includes at
least one transducer, such as an electrochemical or optical
transducer.
In one embodiment, the fluidic system includes detecting or sensing
at least one material from the at least one substrate, extracting
the at least one material in order to analyze and determine a
medical treatment (including preventative, diagnostic, or
responsive), and administering at least one agent. In one
embodiment, the closed loop system is configured in the form of a
patch, bandage, or other attachment vehicle.
In one embodiment, a sensor, such as an enzyme electrode for
glucose, for example, includes a screen-printed electrode on the
surface of which is immobilized glucose oxidase, and an electron
mediator, such as ferrocene or its derivatives. Electrons generated
by the oxidation of glucose are transferred from glucose oxidase to
the electrode by way of the mediator, and the concentration of
glucose is proportional to the current generated. See, for example,
U.S. Pat. No. 7,344,499, which is incorporated herein by reference.
In one embodiment, near-infrared spectroscopy is utilized for
detecting at least one material in at least one substrate. For
example, the concentration of extracted glucose in a gel is
detected by the absorption of the near-infrared light that passes
through the chamber. Id.
In one embodiment, at least one frozen piercing implement is
adapted to include at least one sensor or sensing component. For
example, an enzyme (such as glucose oxidase) can be coated on the
surface of one or more frozen piercing implements, distributed
within the frozen piercing implement, or at least partially filling
an otherwise hollow frozen piercing implement.
In one embodiment, the frozen piercing implement device includes at
least one sensor in communication with at least one electronic
component. In one embodiment, the at least one electronic component
includes at least one of a power source (for example, a battery),
transducer, storage device, display, receiver, or other electronic
component. The at least one electronic component can be included
with at least one piercing implement, support structure,
compartment, or other aspect of the frozen piercing implement
device.
In one embodiment, the at least one sensor can be calibrated by
utilizing the concentration of at least one same or different
analyte, measured by another means. For example, the analyte can be
normalized (by a linear or non-linear relationship), reducing the
variability between analysis events.
In one embodiment, the fluidic device includes at least one
attachment component configured to secure the array device to at
least one substrate. In one embodiment, the at least one attachment
component includes at least one adhesive material.
In one embodiment, the fluidic device includes at least one vacuum
to induce flow in at least one direction through at least one
piercing implement.
In one embodiment, the frozen piercing implement includes at least
one surfactant. In one embodiment, the surfactant includes at least
one ionic surfactant. In one embodiment, the at least one ionic
surfactant includes one or more of an alkyl ammonium salt, bile
acid or salt, fatty acid, carnitine, oligopeptide, polypeptide,
acyl lactylate, mono-diacetylated tartaric acid ester of a
mono-diglyceride, succinylated monoglyceride, citric acid ester of
mono-diglyceride, alginate salt, propylene glycol alginate,
lecithin, hydrogenated lecithin, lysolecithin, hydrogenated
lysolecithin, lysophospholipid, phospholipid, alkylsulfate salt,
fatty acid salt, sodium docusate, or mixtures or derivatives of any
thereof.
Additional Methods, Devices, and Systems for Making and
Administering Frozen Particle Compositions, Frozen Piercing
Implements, and Frozen Piercing Implement Devices
As described herein, a device or machine (including a computer) may
be utilized in various aspects relating to compositions, methods,
or systems relating to one or more frozen particle compositions, or
frozen piercing implements. Non-limiting examples of such aspects
may include predicting or calculating various properties or
characteristics relating to the one or more frozen particle
compositions, or frozen piercing implements, any substrate, any
subject, any administration device, or any administration protocol.
Any method disclosed herein is implicitly intended to also include
"means for" carrying out the method. One or more methods disclosed
include computer-implemented methods.
In one embodiment, a method or means for making one or more frozen
particle compositions, or frozen piercing implements optionally
includes at least one agent. In one embodiment, a method or means
for administering or delivering one or more frozen particle
compositions, or frozen piercing implements is disclosed. In one
embodiment, a method or means for administering at least one frozen
particle composition, or frozen piercing implement includes
administering at least one agent to a substrate.
In one embodiment, at least one computer system is configured to
provide one or more instructions to one or more devices for
deposition or administration of one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, at
least one device is configured to deposit or administer one or more
frozen particle compositions, or frozen piercing implements on any
x, y, or z axis. In one embodiment, the at least one computer
system provides one or more instructions for predicting,
controlling, or varying the administration of one or more frozen
particle compositions, or frozen piercing implements or deposition
of at least one agent included in the one or more frozen particle
compositions, or frozen piercing implements on any x, y, or z
location. In one embodiment, the at least one computer system
provides one or more instructions for temporal, spatial, or
regional locations for deposition or administration of one or more
frozen particle compositions, or frozen piercing implements. Other
components of the at least one computer system or device are
included in the figures as described.
In one embodiment, one or more methods, devices, or systems
described herein include making or administering one or more frozen
particle compositions or frozen piercing implements. In one
embodiment, frozen particle compositions or frozen piercing
implements as described herein are made by one or more processes.
In one embodiment, at least one process described herein is
adaptable for a micro- or nano-scale fabrication of the frozen
particle compositions, or frozen piercing implements. See, for
example, U.S. Patent Application Publication No. 20020193754, which
is incorporated herein by reference.
In one embodiment, a method for making at least one frozen piercing
implement includes etching a frozen composition with a chemical. In
one embodiment, the chemical includes at least one alcohol. In one
embodiment, the alcohol includes at least one of methanol, or
ethanol. In one embodiment, the chemical agent includes at least
one salt or salt solution. In one embodiment, a method for making
at least one frozen piercing implement includes etching a frozen
composition with an acid or a base. In one embodiment, a method for
making at least one frozen piercing implement includes etching a
frozen composition with oxyfuel gas cutting (sometimes referred to
as "flame cutting"). In one embodiment, the base includes sodium
hydroxide, chromium trioxide, ammonium fluoride, ammonium
hydroxide, hydrogen peroxide, or potassium hydroxide.
In one embodiment, the acid includes phenol, acetic acid, nitric
acid, hydrofluoric acid, sulfuric acid, phosphoric acid, or
hydrochloric acid. In one embodiment, a method for making at least
one piercing implement includes etching a frozen composition with
fluid hydrogen oxide (e.g., gas or liquid). In one embodiment, a
method for making at least one piercing implement includes etching
a frozen composition with a fluid form of at least one constituent
of the frozen composition (including but not limited to a frozen
block or film).
In one embodiment, the etching includes a fluid jet stream. For
example, in one embodiment, a water jet cutter is utilized in
etching at least one frozen composition. In one embodiment, the
fluid jet stream includes a gas or liquid jet stream. In one
embodiment, the fluid jet stream includes at least one chemical. In
one embodiment, the at least one chemical includes at least one
agent. In one embodiment, the at least one chemical includes at
least one polymer (e.g., a linear macromolecular partially
hydrolyzed polyacrylamide, such as found in SUPER WATER .TM.,
available from Berkeley Chemical Research, Inc.)
In one embodiment, the fluid jet stream includes air. In one
embodiment, the pressure of the fluid jet stream includes at least
approximately 0.5 psi, approximately 1 psi, approximately 5 psi,
approximately 10 psi, approximately 20 psi, approximately 30 psi,
approximately 40 psi, approximately 50 psi, approximately 60 psi,
approximately 70 psi, approximately 80 psi, approximately 90 psi,
approximately 100 psi, approximately 150 psi, approximately 200
psi, approximately 500 psi, approximately 1,000 psi, approximately
5,000 psi, approximately 10,000 psi, approximately 20,000 psi,
approximately 30,000 psi, approximately 40,000 psi, approximately
50,000 psi, approximately 60,000 psi, approximately 70,000 psi,
approximately 80,000 psi, approximately 90,000 psi, or any value
therebetween or greater. The pressure of the fluid jet stream can
also be adjusted according to other factors, including but not
limited to the width or diameter of the stream, the abrasive flow
rate, or the jet stream traverse rate. See, for example, Srinivasu
and Babu, Appl. Soft Comp. vol. 8, pp. 809-819 (2008), which is
incorporated herein by reference. For example, a narrow jet stream
will generally have greater cutting power than a wider jet stream
due to increased pressure at the nozzle. See, for example, the
world wide web at jetedge.com, the content of which is incorporated
herein by reference.
In one embodiment, the etching includes thermal etching. For
example, crystalline substances can be etched in a saturated air
atmosphere, with an etching time of a few seconds, to several
weeks. See, for example, Krausz and Gold, J of Colloid and
Interface Sci., vol. 25, pp. 255-262 (1967).
In one embodiment, the etching includes laser etching. For example,
frozen piercing implements can be cut from a film, sheet, strip,
block, or other form of frozen composition with an infrared laser.
In one embodiment, the laser is guided by a CAD/CAM design.
In one embodiment, bores are etched (for example, with a physical
or chemical etchant) in the material (such as a frozen composition)
and the remainder of the piercing implement is etched away around
the bores. In one embodiment, the piercing implements and their
bores (if included) are etched simultaneously, or bores are etched
into existing piercing implements.
In one embodiment, bores from the backside of the material (such as
a frozen composition) are generated using a front-to-backside
infrared alignment, and etching from the backside of the
material.
In one embodiment, the etching time includes at least approximately
10 seconds, at least approximately 20 seconds, at least
approximately 30 seconds, at least approximately 1 minute, at least
approximately 5 minutes, at least approximately 10 minutes, at
least approximately 20 minutes, at least approximately 30 minutes,
at least approximately 2 hours, at least approximately 5 hours, at
least approximately 10 hours, at least approximately 24 hours, at
least approximately 2 days, at least approximately 5 days, at least
approximately 1 week, at least approximately 2 weeks, at least
approximately 3 weeks, at least approximately 1 month, at least
approximately 3 months, or any value therebetween. Various factors
can influence the etching time required, including but not limited
to at least one of: etching temperature, etching chemical,
constitution of material being etched, thickness of material being
etched, or desired characteristic of the frozen piercing
implement(s).
The etched radius for a particular composition can be controlled by
varying the etchant (e.g., chemical, thermal, or other), the amount
of time exposed to the etchant, the temperature of the etchant or
etching environment, the constituency of the composition being
etched, desired size, or shape of the etching, thickness of the
composition being etched, or other factors.
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are designed with the aid of a computer
device, computer system, computer program product, or
computer-implemented method. In one embodiment, the frozen particle
compositions, or frozen piercing implements, are generated with the
aid of a computer device, computer system, computer program
product, or computer-implemented method. In one embodiment, the
frozen particle compositions, or frozen piercing implements, are
administered with the aid of a computer device, computer system,
computer program product, or computer-implemented method.
In one embodiment, a simulation for a mask is generated, optionally
with assistance from a computer device, computer system, computer
program product, or computer-implemented method. See, for example,
Wilke et al., Euro. Micro & Nano Systems 20-21 (2004), which is
incorporated herein by reference. As discussed by Wilke et al., a
mask can be designed on the basis of a Simode simulation, and
optical microscopy as well as scanning electron microscopy can be
utilized to examine single microneedles resulting from the etching
process. Id. Thus, by varying the etching times, temperatures, and
other factors, microneedles can be consistently reproduced with
high accuracy. Id. In one embodiment, an array device including a
plurality of microneedles can be generated that can be peeled off
for use. Id.
In one embodiment, a thermal etchant is utilized for fabricating
one or more frozen piercing implements. In one embodiment, a fluid
jet (e.g., gas or liquid) is utilized for etching one or more
frozen piercing implements. In one embodiment, a laser beam is
utilized for etching one or more frozen piercing implements. In one
embodiment, an electron beam is utilized for etching one or more
frozen piercing implements. In one embodiment, an ion beam is
utilized for etching one or more frozen piercing implements.
In one embodiment, at least one frozen fluid (including but not
limited to at least one solid condensed gas) is deposited onto a
cryogenically cooled support surface (e.g., metal, or silicon
surface) in the chamber of a combined scanning electron microscope
and focused ion beam apparatus (FEI Co., Hillsboro, OR). See, for
example, King et al, Nano Lett. vol. 5, pp. 1157-1160 (2005), which
is herein incorporated by reference. Next, the ice surface is
exposed to focused energetic electron or gallium ion beams, which
stimulates local removal of ice. Id. In one embodiment, the beams
are programmed to produce at least one pattern in the ice. Id.
Additional ice can be removed by in situ sublimation (e.g., by
eliminating liquid surface tension effects) by fluid jet, or by
other means. Id.
In one embodiment, the ice is deposited at a rate of approximately
1 pm/second, approximately 1 nm/second, approximately 1 mm/second,
approximately 1 cm/second, or any value therebetween. In one
embodiment, the ice is deposited using a leak valve controlled
vapor flow that is directed onto the cooled support surface or
sample. In one embodiment, the cooled sample or cooled support
surface is maintained at approximately 128 K (approximately
-145.degree. C.). Id. In one embodiment, the fluid includes
hydrogen oxide. In one embodiment, the hydrogen oxide is deposited
on the cooled support surface by way of a magnesium sulfate-water
vapor source, and water vapor pressure is controlled by at least
one leak valve. Id.
In one embodiment, the etching system includes at least one cold
finger located near the sample surface to ensure a sufficient
thermal gradient to keep unwanted species from condensing on the
support surface or sample surface. Id. In one embodiment, the cold
finger is placed approximately 1 mm from the surface, approximately
2 mm from the surface, approximately 3 mm from the surface,
approximately 4 mm from the surface, approximately 5 mm from the
surface, approximately 6 mm from the surface, approximately 7 mm
from the surface, approximately 8 mm from the surface,
approximately 9 mm from the surface, approximately 10 mm from the
surface, approximately 1 cm from the surface, approximately 1 dm
from the surface, or any value therebetween. In one embodiment, the
temperature of the sample surface can be controlled within
approximately +/-1 K (approximately +/-1 degree C.). Id. In one
embodiment, scanning electron microscopy can be utilized to observe
etching of the frozen fluid composition. Id.
In one embodiment, the laser beam includes at least one of a carbon
dioxide laser, or a Erbium:YAG laser. See, for example, U.S. Patent
Application Publication No. 20080290065, which is herein
incorporated by reference. Erbium:YAG lasers are commonly used in
the medical sector, since the laser beam pinpoints the maxium
absorption spike of water. Id. In one embodiment, the laser beam
(e.g., carbon dioxide, erbium:YAG, eximer, argon, KTP, krypton
fluoride, xenon chloride, xenon fluoride, helium neon,
neodynmium:YAG, erbium glass, erbium: YAG, holmium:YAG, Ruby
(chromium sapphire), gallium arsenide, or other) etches a frozen
fluid by way of explosive vaporization. Id.
In one embodiment, the laser type is selected based on the
absorption wavelength of laser energy by the frozen composition.
Such an absorption profile can be generated, if not already known,
using standard techniques.
In one embodiment, the laser beam is part of an etching system for
forming one or more frozen piercing implements. In one embodiment,
the laser system includes at least one first mirror that is
optionally connected to at least one first driver under command of
at least one controller. In one embodiment, the laser system
includes at least one second mirror that is optionally connected to
at least one second driver under command of at least one
controller. In one embodiment, the at least one first driver and
the at least one second driver are the same driver. In one
embodiment, the at least one first driver and the at least one
second driver are different drivers. In one embodiment, at least
one of the at least one first driver or the at least one second
driver includes at least one of a servo-galvanometer driver device,
or a stepper motor driver device. Id.
In one embodiment, the at least one first mirror controls x-axis
positioning of the laser. In one embodiment, the at least one
second mirror controls y-axis positioning of the laser. In one
embodiment, the etching system includes at least one third mirror.
In one embodiment, the at least one third mirror is configured to
operate as a shutter for directing the laser beam away from the
material to be etched. In one embodiment, the laser system includes
one or more instructions for etching the frozen material into one
or more frozen piercing implements.
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by pouring a liquid suspension,
solution, or mixture, of the desired constituents into a vessel,
mold or frame, and optionally completing the filling under vacuum.
See, for example, Park et al., Pharm Res. vol. 23, no. 5 (2006),
which is incorporated herein by reference. Following filling the
mold, the constituents of the mold are optionally concentrated by
way of evaporation or other process. Id. Next, the mold is frozen
under conditions and time sufficient to at least partially solidify
the constituents of the mold. Finally, the frozen particle
compositions, or frozen piercing implements, are released from the
vessel, mold or frame. Id.
As discussed herein, the conditions and time sufficient to at least
partially solidify at least one fluid includes the particular
points of state function or phase transition for the fluid. For
example, first-order phase transitions involve a latent heat.
During a first-order phase transition, the system either absorbs or
releases a fixed amount of energy, and the temperature of the
system stays constant as heat is added. In another example,
second-order phase transitions have no associated latent heat, such
as the glass transition of polymeric materials at the glass
transition temperature of the polymer. The glass transition
temperature can be measured by the change in the slope of the
heating energy versus temperature curve that results from the
measurement on a differential scanning calorimetry device.
Accordingly, a fluid composition's phase or state varies with
certain parameters of the conditions sufficient to at least
partially solidify the fluid composition. For example, the state
variables of pressure and temperature assist to define specific
conditions sufficient to at least partially solidify a particular
fluid.
As discussed herein, the mold or frame can be made from any
material that allows fabrication of the frozen piercing implements.
In one embodiment, the mold or frame itself is frozen. In one
embodiment, the mold or frame includes at least one metal, glass,
or plastic. In one embodiment, the mold or frame is disposable. In
one embodiment, the mold or frame is reusable.
In one embodiment, the frozen particle compositions, or frozen
piercing implements are spray or dip coated with at least one
agent. Id. In one embodiment, the at least one agent includes at
least one adhesive agent, therapeutic agent, reinforcement agent,
biological remodeling agent, abrasive, or explosive material.
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by layer deposition on a
support structure (which may or may not be frozen).
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by drawing lithography. See,
for example, WO2008010682, which is incorporated herein by
reference. In one embodiment, the frozen particle compositions, or
frozen piercing implements, are fabricated as solid or hollow
compositions by laying down a frozen composition on the surface of
a support structure, and removing the implement.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by spraying at least one fluid
composition into at least one compartment. In one embodiment, the
at least one compartment includes at least one fluid. In one
embodiment, the at least one fluid includes at least one gas or
liquid. In one embodiment, the at least one fluid includes at least
one supercooled liquid. In one embodiment, the at least one liquid
includes liquid nitrogen, liquid carbon dioxide, liquid argon,
liquid helium, or other inert or reactive liquid. In one
embodiment, the at least one fluid includes at least one of liquid
nitrogen, liquid carbon dioxide, liquid hydrogen, liquid oxygen,
liquid helium, liquid methane, methane/ammonia, a halogenated
hydrocarbon, liquid neon, liquid argon, liquid mercury, air, cold
saline, cold sodium hydroxide, cold potassium hydroxide, cold
potassium chloride, cold sodium chloride solution, or hydrogen
sulfide. In one embodiment, the at least one fluid includes at
least one of tetrachloromethane; trichlorofluoromethane;
dichlorodifluoromethane; bromochlorodifluoromethane;
dibromodifluoromethane; chlorotrifluoromethane;
bromotrifluoromethane; carbon tetrafluoride; trichloromethane;
dichlorofluoromethane; chlorodifluoromethane; bromodifluoromethane;
drifluoromethane; dichloromethane; chloromethane; fluoromethane;
methane; hexachloroethane; pentachlorofluoroethane;
1,1,2,2,-tetrachloro-1,2-difluoroethane;
1,1,1,2-tetrachloro-2,2-difluoroethane;
1,1,2-trichlorotrifluoroethane; 1,1,1-trichlorotrifluoroethane;
1,2-dichlorotetrafluoroethane; 1,1-dichlorotetrafluoroethane;
dibromoetetrafluoroethane; chloropentafluoroethane;
hexafluoroethane; pentachloroethane;
1,1,2,2-tetrachloro-1-fluoroethane;
1,1,2-trichloro-2,2-difluoroethane;
1,1,2-trichloro-1,2-difluoroethane;
1,1,1-trichloro-2,2-difluoroethane;
2,2-dichloro-1,1,1-trifluoroethane;
1,2-dichloro-1,1,2-trifluoroethane;
1,1-dichloro-1,2,2-trifluoroethane;
2-chloro-1,1,2,2-tetrafluoroethane; pentafluoroethane;
(difluoromethoxy)(trifluoro)methane; 1,1,2,2-tetrachloroethane;
1,1,1,2-tetrachloroethane; 1,1,2-trichloro-2-fluoroethane;
1,1,2-trichloro-1-fluoroethane; 1,1,1-trichloro-2-fluoroethane;
dichlorodifluoroethane; 1,1,-dichloro-2,2-difluoroethane;
1,2-dichloro-1,1-difluoroethane; 1,1-dichloro-1,2-difluoroethane;
1,2-dibromo-1,1-difluoroethane; 1-chloro-1,2,2-trifluoroethane;
1-chloro-2,2,2-trifluoroethane; 1-chloro-1,1,2-trifluoroethane;
1,1,2,2-tetrafluoroethane; 1,1,1,2-tetrafluoroethane,
bis(difluoromethyl)ether; 1,1,2-trichloroethane;
1,1,1-trichloroethane; 1,2-dichloro-1-fluoroethane;
1,2-dibromo-1-fluoroethane; 1,1-dichloro-1-fluoroethane;
chlorodifluoroethane; 1-chloro-1,2-difluoroethane;
1-chloro-1,1-difluoroethane; 1,1,2-trifluoroethane;
1,1,1-trifluoroethane; methyl trifluoromethyl ether;
2,2,2-trifluoroethyl methyl ether; 1,2-dichloroethane;
1,1-dichloroethane; chlorofluoroethane; 1-chloro-1-fluoroethane;
1,2-difluoroethane; 1,1-difluoroethane; chloroethane; fluoroethane;
ethane; 1,1,1,2,2,3,3-heptachloro-3-fluoropropane;
hexachlorodifluoropropane;
1,1,1,3,3-pentachloro-2,2,3-trifluoropropane;
1,2,2,3-tetrachloro-1,1,3,3-tetrafluoropropane,
1,1,1-trichloro-2,2,3,3,3-pentafluoropropane;
1,2-dichloro-1,1,2,3,3,3-hexafluoropropane;
1,3-dichloro-1,1,2,2,3,3-hexafluoropropane;
1-chloro-1,1,2,2,3,3,3-heptafluoropropane;
2-chloro-1,1,1,2,3,3,3-heptafluoropropane; octafluoropropane;
1,1,1,2,2,3-hexachloro-3-fluoropropane; pentachlorodifluoropropane;
1,1,1,3,3-pentachloro-2,2-difluoropropane,
tetrachlorotrifluoropropane;
1,1,3,3-tetrachloro-1,2,2-trifluoropropane;
1,1,1,3-tetrachloro-2,2,3-trifluoropropane;
trichlorotetrafluoropropane;
1,3,3-trichloro-1,1,2,2-tetrafluoropropane;
1,1,3-trichloro-1,2,2,3-tetrafluoropropane;
1,1,1-trichloro-2,2,3,3-tetrafluoropropane;
dichloropentafluoropropane;
2,2-dichloro-1,1,1,3,3-pentafluoropropane;
2,3-dichloro-1,1,1,2,3-pentafluoropropane;
1,2-dichloro-1,1,2,3,3-pentafluoropropane;
3,3-dichloro-1,1,1,2,2-pentafluoropropane;
1,3-dichloro-1,1,2,2,3-pentafluoropropane;
1,1-dichloro-1,2,2,3,3-pentafluoropropane;
1,2-dichloro-1,1,3,3,3-pentafluoropropane;
1,3-dichloro-1,1,2,3,3-pentafluoropropane;
1,1-dichloro-1,2,3,3,3-pentafluoropropane; chlorohexafluoropropane;
2-chloro-1,1,1,2,3,3-hexafluoropropane;
3-chloro-1,1,1,2,2,3-hexafluoropropane;
1-chloro-1,1,2,2,3,3-hexafluoropropane;
2-chloro-1,1,1,3,3,3-hexafluoropropane;
1-chloro-1,1,2,3,3,3-hexafluoropropane;
1,1,2,2,3,3,3-heptafluoropropane; trifluoromethyl
1,1,2,2-tetrafluoroethyl ether; 1,1,1,2,3,3,3-heptafluoropropane;
trifluoromethyl 1,2,2,2-tetrafluoroethyl ether;
pentachlorofluoropropane; tetrachlorodifluoropropane;
1,1,3,3-tetrachloro-2,2-difluoropropane;
1,1,1,3-tetrachloro-2,2-difluoropropane; trichlorotrifluoropropane;
1,1,3-trichloro-2,2,3-trifluoropropane;
1,1,3-trichloro-1,2,2-trifluoropropane;
1,1,1-trichloro-2,2,3-trifluoropropane; dichlorotetrafluoropropane;
2,2-dichloro-1,1,3,3-tetrafluoropropane;
2,2-dichloro-1,1,1,3-tetrafluoropropane;
1,2-dichloro-1,2,3,3-tetrafluoropropane;
2,3-dichloro-1,1,1,2-tetrafluoropropane;
1,2-dichloro-1,1,2,3-tetrafluoropropane;
1,3-dichloro-1,2,2,3-tetrafluoropropane;
1,1-dichloro-2,2,3,3-tetrafluoropropane;
1,3-dichloro-1,1,2,2-tetrafluoropropane;
1,1-dichloro-1,2,2,3-tetrafluoropropane;
2,3-dichloro-1,1,1,3-tetrafluoropropane;
1,3-dichloro-1,1,3,3-tetrafluoropropane;
1,1-dichloro-1,3,3,3-tetrafluoropropane; chloropentafluoropropane;
1-chloro-1,2,2,3,3-pentafluoropropane;
3-chloro-1,1,1,2,3-pentafluoropropane;
1-chloro-1,1,2,2,3-pentafluoropropane;
2-chloro-1,1,1,3,3-pentafluoropropane;
1-chloro-1,1,3,3,3-pentafluoropropane;
1,1,1,2,2,3-hexafluoropropane; 1,1,1,2,3,3-hexafluoropropane;
1,1,1,3,3,3-hexafluoropropane; 1,2,2,2-tetrafluoroethyl
difluoromethyl ether; hexafluoropropane; tetrachlorofluoropropane;
trichlorodifluoropropane; dichlorotrifluoropropane;
1,3-dichloro-1,2,2-trifluoropropane;
1,1-dichloro-2,2,3-trifluoropropane;
1,1-dichloro-1,2,2-trifluoropropane;
2,3-dichloro-1,1,1-trifluoropropane;
1,3-dichloro-1,2,3-trifluoropropane;
1,3-dichloro-1,1,2-trifluoropropane; chlorotetrafluoropropane;
2-chloro-1,2,3,3-tetrafluoropropane;
2-chloro-1,1,1,2-tetrafluoropropane;
3-chloro-1,1,2,2-tetrafluoropropane;
1-chloro-1,2,2,3-tetrafluoropropane;
1-chloro-1,1,2,2-tetrafluoropropane;
2-chloro-1,1,3,3-tetrafluoropropane;
2-chloro-1,1,1,3-tetrafluoropropane;
3-chloro-1,1,2,3-tetrafluoropropane;
1-chloro-1,1,1,2-tetrafluoropropane;
1-chloro-1,1,2,3-tetrafluoropropane;
3-chloro-1,1,1,3-tetrafluoropropane;
1-chloro-1,1,3,3-tetrafluoropropane; 1,1,2,2,3-pentafluoropropane;
pentafluoropropane; 1,1,2,3,3-pentafluoropropane;
1,1,1,2,3-pentafluoropropane; 1,1,1,3,3-pentafluoropropane; methyl
pentafluoroethyl ether; difluoromethyl 2,2,2-trifluoroethyl ether;
difluoromethyl 1,1,2-trifluoroethyl ether; trichlorofluoropropane;
dichlorodifluoropropane; 1,3-dichloro-2,2-difluoropropane;
1,1-dichloro-2,2-difluoropropane; 1,2-dichloro-1,1-difluoropropane;
1,1-dichloro-1,2-difluoropropane; chlorotrifluoropropane
2-chloro-1,2,3-trifluoropropane; 2-chloro-1,1,2-trifluoropropane;
1-chloro-2,2,3-trifluoropropane; 1-chloro-1,2,2-trifluoropropane;
3-chloro-1,1,2-trifluoropropane; 1-chloro-1,2,3-trifluoropropane;
1-chloro-1,1,2-trifluoropropane; 3-chloro-1,3,3-trifluoropropane;
3-chloro-1,1,1-trifluoropropane; 1-chloro-1,1,3-trifluoropropane;
1,1,2,2-tetrafluoropropane; methyl 1,1,2,2-tetrafluoroethyl ether;
dichlorofluoropropane; 1,2-dichloro-2-fluoropropane;
chlorodifluoropropane; 1-chloro-2,2-difluoropropane;
3-chloro-1,1-difluoropropane; 1-chloro-1,3-difluoropropane;
trifluoropropane; chlorofluoropropane; 2-chloro-2-fluoropropane;
2-chloro-1-fluoropropane; 1-chloro-1-fluoropropane;
difluoropropane; fluoropropane; propane;
dichlorohexafluorocyclobutane; chloroheptafluorocyclobutane;
octafluorocyclobutane; decafluorobutane; perfluoropropyl methyl
ether; perfluoroisopropyl methyl ether;
1,1,1,3,3-pentafluorobutane; tetradecafluorohexane; butane;
isobutane; pentane; isopentane; diethyl ether; methyl formate;
methylamine; ethylamine; nitrous oxide; sulfur dioxide; krypton;
1,1-dichloro-2,2-difluoroethylene; chlorotrifluoroethylene;
tetrafluoroethylene; trichloroethylene; cis-1,2-dichloroethylene;
1,1-difluoroethylene; chloroethylene; fluoroethylene; ethylene;
hexafluoropropylene; hexafluoropropene trimer; propylene;
hydrofluorocarbon; chlorofluorocarbon; hydrochlorofluorocarbon; or
the like.
In one embodiment, the at least one fluid composition is sprayed
beneath the surface of the fluid bath. In one embodiment, the at
least one fluid composition is sprayed just above the surface of
the fluid bath. In one embodiment, at least one mechanism is
utilized to form or break up frozen compositions into frozen
particle compositions, or frozen piercing implements. In one
embodiment, the at least one mechanism includes at least one of
vibration, physical mixing, bubble mixing, or sonication. See, for
example, U.S. Pat. No. 4,704,873, which is incorporated herein by
reference.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by spraying at least one fluid
composition into at least one freezing chamber by way of at least
one inlet port, whereby as the at least one fluid composition
travels through the chamber, the at least one fluid droplets freeze
into solid particles. In one embodiment, the at least one freezing
chamber includes at least one carrier gas. In one embodiment, the
at least one freezing chamber is held under a vacuum. In one
embodiment, the at least one fluid composition particles travel
through the freezing chamber by at least one force including
gravity, magnetism, electrostatic energy, electromagnetic energy,
centrifugal force, centripetal force, capillary action, hydrophobic
or hydrophilic attraction or repulsion, van der Waals forces, or
other force. In one embodiment, the one or more frozen particle
compositions, or frozen piercing implements are collected by at
least one outlet port. See, for example, U.S. Pat. No. 5,219,746,
which is incorporated herein by reference.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by utilizing a system for
continuously or serially making and administering the one or more
frozen particle compositions or frozen piercing implements. In one
embodiment, the system includes at least one device for making one
or more frozen particle compositions or frozen piercing implements
and at least one device for administering one or more frozen
particle compositions or frozen piercing implements. In one
embodiment, the system includes at least one hose connecting the at
least one device for making and the at least one device for
administering the one or more frozen particle compositions or
frozen piercing implements. In one embodiment, the system includes
at least one carrier gas. In one embodiment, the at least one
device for administering the one or more frozen particle
compositions or frozen piercing implements includes at least one
handheld or portable device. In one embodiment, the at least one
handheld device includes at least one propulsion gun.
In one embodiment, the device includes at least one component for
directing administration of the at least one frozen particle
composition or at least one frozen piercing implement. In one
embodiment, the at least one component includes at least one
nozzle. In one embodiment, the at least one nozzle includes at
least one de Laval nozzle.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements move at least partially through the
delivery device by way of Venturi effect.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by utilizing an extrusion
process in a chamber maintained under pressure, and including at
least one carrier gas for administration of the frozen particle
compositions or frozen piercing implements. See, for example, U.S.
Pat. No. 5,666,821, which is incorporated herein by reference.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by utilizing at least one
cutting mechanism with at least one frozen fluid or frozen
composition substantially in the form of a block, ribbon, sheet, or
other form. See, for example, U.S. Pat. Nos. 5,913,711; and
5,520,572, each of which is incorporated herein by reference.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by grinding or pulverizing at
least one frozen composition. In one embodiment, at least one
frozen composition is ground with an auger and delivered under
pressure with at least one carrier gas. See, for example, U.S. Pat.
No. 6,174,225, which is incorporated herein by reference.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by utilizing an ink jet style
printer. See, for example, U.S. Pat. No. 7,306,316, which is
incorporated herein by reference. In one embodiment, the ink jet
style printer utilizes at least one supercooled fluid. In one
embodiment, the supercooled fluid includes at least one cryogenic
fluid. In one embodiment, the ink jet style printer includes a
non-direct contact mechanism for administering the one or more
frozen particle compositions or frozen piercing implements to at
least one substrate. In one embodiment, the ink jet style printer
includes at least one chamber under a vacuum.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are made by utilizing a rotary device.
See, for example, U.S. Pat. No. 4,703,590, which is incorporated
herein by reference. In one embodiment, the rotary device provides
at least one mold. In one embodiment, at least one fluid
composition is introduced to the at least one mold, and while the
rotary device rotates through a freezing chamber, the at least one
fluid composition in the at least one mold becomes at least
partially frozen. As the rotary device rotates further, the at
least one frozen particle composition exits the at least one
mold.
In one embodiment, the one or more frozen particle compositions or
frozen piercing implements are made by utilizing a "pelletizer."
See, for example, U.S. Pat. No. 4,617,064, which is incorporated
herein by reference. In one embodiment, the one or more frozen
particle compositions or frozen piercing implements are made, for
example, by utilizing a holding tank, cooling reservoir,
compressor, and delivery device with a carrier gas. See, for
example, U.S. Pat. No. 6,306,119, which is incorporated herein by
reference.
In one embodiment, the one or more frozen particle compositions or
frozen piercing implements are made by depositing at least one
fluid composition on at least one support surface. In one
embodiment, a screen-like material, for example, a nonperforated
sheet, strip, or plane receives atomized droplets (e.g. water
droplets), which are then frozen to form ice crystals. See, for
example, U.S. Pat. No. 6,764,493, which is incorporated herein by
reference. In one embodiment, a wire mesh screen moves through a
temperature controlled water bath that coats the mesh with a thin
water layer. Id. In one embodiment, as the mesh enters the cold
environment, ice crystals form and are brushed or scraped from the
mesh with a brush. Id. In one embodiment, temperature and pressure
sensors within the vessel can be used by the control device to
adjust carrier fluid temperature and input pressure. Id.
In one embodiment, the one or more frozen particle compositions or
frozen piercing implements are made by extruding at least one fluid
composition through at least one aperture, die or nozzle. See, for
example, U.S. Pat. No. 6,986,265, which is incorporated herein by
reference. In one embodiment, the nozzle includes at least one de
Laval nozzle. In one embodiment, at least one frozen composition in
the form of a ribbon, block, or sheet, for example, is passed
through the at least one aperture, die or nozzle. In one
embodiment, at least one fluid composition is provided to a
freezing chamber configured to freeze the at least one fluid
composition, and subsequently extruded.
In one embodiment, the one or more frozen particle compositions or
frozen piercing implements are administered to at least one
substrate. In one embodiment, the one or more frozen particle
compositions or frozen piercing implements are administered by way
of compressed gas, blast plate, high-speed rotor, or electrostatic
acceleration (e.g., subatomic accelerators). See, for example, U.S.
Pat. No. 4,945,050, which is incorporated herein by reference.
In one embodiment, one or more frozen particle compositions or one
or more frozen piercing implements are made by utilizing
electrospray techniques. In one embodiment, electrospray techniques
are conducted in a vacuum. See, for example, Castro and Bocanegra,
Applied Phys. Lett. vol. 88, pp. 123105-1-123105-3; and U.S. Pat.
No. 2,048,651, each of which is incorporated herein by reference.
In one embodiment, electrospray techniques provide a narrow drop
size distribution, whose mean diameter can be controlled from at
least tens of nanometers to at least hundreds of microns. Id. In
one embodiment, two concentric needles are fed with the conducting
fluid and non-aqueous fluids through inner and outer needles,
respectively. Id. In one embodiment, when an electric field is
applied, the free charges in the conducting fluid migrate to the
interface with the non-aqueous fluid. Id. In one embodiment, the
flow-rates fed to the needles is controllable, which allows for
varying contributions from the conducting fluid or non-aqueous
constituents. Id. In one embodiment, colloidal propulsion
efficiency depends on the ratio of mass vs. charge of the droplets.
Id. When a conducting fluid surface is charged to a sufficiently
high electrical potential, the interface generally forms a cone,
usually referred to as a Taylor cone. Id. A Taylor cone of hydrogen
oxide held in a vacuum freezes almost immediately. Id. However,
when the conducting liquid includes hydrogen oxide, and the
non-aqueous fluid includes at least one oil, a Taylor cone exists
in a vacuum without freezing. Id. Thus, electrospray conditions can
be modified according to the constituents of the frozen particle
compositions, or frozen piercing implements.
In one embodiment, electrospraying is conducted by exposing fibers
of viscous fluid composition to static electricity having one pole
electrically connected with the fluid composition and the opposite
pole electrically connected with at least one collection surface.
See, for example, U.S. Pat. No. 2,048,651, which is incorporated
herein by reference. In one embodiment, the viscous fluid
composition includes a cold fluid composition. In one embodiment,
the collection surface is approximately at or below the freezing
point of the at least one fluid composition.
In one embodiment, one or more methods described herein can be
utilized for fabricating one or more of frozen piercing implements,
frozen piercing implement devices, including but not limited to
frozen piercing implement arrays, fluidic devices, or injection
devices, or other associated frozen tools and devices thereof.
As described herein, general fabrication techniques can be
utilized, or adapted for making frozen particle compositions,
including frozen piercing implements. Examples of such fabrication
techniques include form-molding, etching, deposition,
micromachining, and freeze-mixing. In one embodiment, the one or
more frozen piercing implements are fabricated by utilizing
multiple processes.
In one embodiment, one or more frozen piercing implements are
fabricated by utilizing electrochemical etching. In one embodiment,
a frozen composition (e.g., in block, ribbon, or sheet form) is
masked for areas of piercing implements, and etched utilizing at
least one electrolytic solution. In one embodiment, the
electrolytic solution is cold, to prevent disintegration or
dissolution of the frozen composition. In one embodiment, the
electroylytic solution includes at least one of sodium, potassium,
fluoride, chloride, bromide, calcium, magnesium, hydrogen
phosphate, or hydrogen carbonate.
In one embodiment, one or more frozen piercing implements are
formed by splintering or abrading a frozen composition. For
example, a frozen composition block or ribbon can be splintered or
abraded by utilizing a machine that includes at least one abrading
wheel, or annular splint carrier. See, for example, U.S. Pat. No.
1,613,623, which is herein incorporated by reference.
In one embodiment, frozen piercing implements are formed by
utilizing a frozen composition and a lithography process. In one
embodiment, the lithography process includes at least
photolithography. In one embodiment, the lithography process
includes at least electron beam lithography. In one embodiment,
etching includes wet etching or dry etching. For example, wet
etching can utilize chemicals alone or in combination with an
energy source, to at least partially remove material surrounding a
device, or to remove one or more layers from the surface of the
material to be etched. In one embodiment, the frozen composition is
a film or block.
In one embodiment, etching includes plasma etching or reactive ion
etching. For example, reactive ion etching includes introducing at
least one etching gas into the chamber with the composition to be
etched. In one embodiment, plasma is created by radiofrequency
power, and reactive species (radicals and ions) are generated in
the plasma. In one embodiment, reactive species diffuse onto the
surface of the composition, while byproducts from the chemical
reaction are desorbed and exhausted from the chamber. In one
embodiment, the reactive ion etching system includes at least one
of a parallel plate etching configuration with at least one
electrode (e.g. 5 inch quartz electrode), and at least one radio
frequency generator (e.g. 1 kW, 15 MHz). See, for example, U.S.
Patent Application Publication No. 20020193754, which is herein
incorporated by reference. In one embodiment, the system further
includes at least one of a mass flow controller, throttle valve,
controller, or vacuum pump. Id. In one embodiment, reactive ion
etching removes at least one layer of material to be etched.
In one embodiment, etching includes isotropic etching or
anisotropic etching. In one embodiment, undercutting is used to
remove material from under a mask. In one embodiment, undercutting
is conducted with at least one of a chemical, a mechanical force,
an electromagnetic force, an electrical force, a thermal change, or
a combination thereof. In one embodiment, undercutting is conducted
with a laser, or fluid jet beam. In one embodiment, undercutting is
conducted by a thermal source (including but not limited to
conduction, convection, or radiation).
In one embodiment, a masking material is deposited onto a frozen
composition and patterned into dots having a diameter approximately
equal to the base of the desired frozen piercing implements. The
frozen composition is then subjected to etching by a standard
method, some of which are described herein. The regions protected
by the mask remain and form the frozen piercing implements. In one
embodiment, the mask is insulative. In one embodiment, the mask is
heated or chemically treated. In one embodiment, etching continues
until the mask falls off due to underetching, thereby generating an
array of frozen piercing implements.
In one embodiment, a "donut-shaped" mask is utilized to etch hollow
frozen piercing implements with inner and outer walls being etched
simultaneously. See, for example, U.S. Pat. No. 6,334,856, which is
incorporated herein by reference.
In one embodiment, a robotic array-spotting device (e.g., DNA
microarrayer) is utilized to generate droplets. See, for example,
Park et al., Biomed Devices, vol. 11, pp. 129-133 (2009), which is
incorporated herein by reference. In one embodiment, the droplets
are approximately uniform in size or position. In general,
microarrayers can generate many identical liquid droplets on a
support structure. Id. In addition, the droplets generally have
high resolution and droplet volume can be controlled. Id. In one
embodiment, a microarrayer can generate greater than approximately
one thousand droplets per square centimeter. Id. Subsequently, the
droplets are frozen, and fabricated into frozen piercing
implements. In one embodiment, a channel network is made by placing
a thin wire (e.g., metal wire) on a flat surface, dropping droplets
onto the wire, and freezing the droplets, forming wells along the
wire channel. Id. In one embodiment, the channel network is
utilized in at least one array device, or fluidic device described
herein.
In one embodiment, frozen piercing implements are fabricated by
utilizing a micromold having tapered walls. For example, a
micromold can be made, for example, by molding a pre-existing
3-dimensional array of microneedles or other piercing implements.
The micromold is then surface plated or coated by, for example,
vapor deposition of one or more constituents. In one embodiment, at
least one constituent is spin-cast in the micromold and frozen. In
one embodiment, a micromold can be made, for example, by laser
ablation techniques.
In one embodiment, the constituents of the composition (i.e., at
least one fluid and at least one agent) are combined and blended in
at least one polymer (e.g., cellulose, polylactic acid,
polyglycolic acid, or copolymers thereof, etc.), binder, or
pharmaceutical carrier or excipient. Next, the composition is spun
in a mold (e.g., a micromold or nanomold), defining at least one
cavity at 3000 rpm for 5 minutes. See, for example, Oh and Kwon,
CRS conference presentation (2007), which is incorporated herein by
reference. In one embodiment, at least two cavities of the mold are
loaded with at least two different compositions. Next, the
compositions are at least partly frozen prior to, during, or
subsequent to spin-casting. The composition on the exterior of the
cavities is optionally removed following centrifugation. Id. In the
spun-cast system, the higher density substances will be forced
toward the top (e.g. tip) of the piercing implements. Id.
Devices including at least one frozen piercing implement can also
be fashioned, for example, utilizing a mold (e.g., micromold, or
nanomold). See, for example, Park et al, Ibid.
In one embodiment, for example, the mold is fabricated from an
epoxy (e.g. using high-aspect-ratio SU-8 epoxy photoresist master
structures to form polydimethyl siloxane molds). In one embodiment,
injection molding is utilized for fabricating the piercing
implements from the molds. Id. In one embodiment, an asymmetric
masking process during etching of the mold is utilized to form
beveled or other shaped tips. Id. In one embodiment, microlenses
are utilized for fabricating the molds (which can be altered by
changing the focal point of the microlens). Id.
In one embodiment, the frozen piercing implement support structure
includes a hydrophobic, super hydrophobic, omniphobic, hydrophilic,
or amphiphilic surface. In one embodiment, the support structure
includes a polymeric surface. In one embodiment, the support
structure includes one or more of glass, plastic, metal, or at
least one frozen material. In one embodiment, the support structure
includes at least one of silicon, copper, silver, gold, platinum,
rubidium, or polytetrafluoroethylene.
In one embodiment, the surface of a support structure is coated
with a fluid (including a viscous form) of at least one
constitutent of the final frozen implement. In one embodiment, a
mold or frame is configured with at least one characteristic for
fabricating the piercing implement. For example, the at least one
characteristic may include but not be limited to the desired size,
shape, optional one or more ports, outer diameter, inner diameter
(for hollow or partially hollow implements), length, inclination
angle of at least one side, array pattern, etc. In one embodiment,
the mold or frame is includes a comb-like configuration. In one
embodiment, the mold or frame is then drawn into the fluid
constituent material. In one embodiment, the mold or frame itself
is coated with the fluid constituent material. In one embodiment,
the fluid constituent material is frozen while it is drawn with the
mold or frame. In one embodiment, the drawing process is carried
out by fixing the support structure and moving the mold or frame
upward or downward, or by fixing the mold or frame, and drawing the
support structure upward or downward. In one embodiment, at least
one desired characteristic of the piercing implements can be
fabricated by varying the drawing speed, or by shaping or cutting
with a mechanical cutter, electrical cutter, magnetic cutter,
thermal cutter, or cutter of another source. In one embodiment, the
cutter includes a laser beam.
In one embodiment, the frozen piercing implements are evaporated
before removing from the mold or frame. In one embodiment, at least
one additional layer is applied to the frozen piercing implements
by, for example, vapor deposition, spray coating, dip coating, or
other process.
In one embodiment, the frozen piercing implements are removed from
the mold or frame by varying the humidity, pressure, or temperature
of the piercing implements or the mold or frame. In one embodiment,
the mold or frame is heated to release the implements. In one
embodiment, the mold or frame is fashioned such that it can be
adapted to be heated by electrical, mechanical, thermal,
electromagnetic, or other source of heat. In one embodiment, the
mold or frame includes a hand-in-glove configuration.
In one embodiment, at least one heater heats the mold or frame by
way of conduction, convection, or radiation. In one embodiment, the
mold or frame is coated (for example, with a polymer, oil, wax,
film, etc.) for easier removal of the piercing implements. In one
embodiment, the mold or frame is coated with
polytetrafluoroethylene.
In one embodiment, the frozen piercing implements are removed from
the mold or frame by applying at least one solvent to the mold,
frame, or frozen piercing implements. In one embodiment, the
solvent includes a liquid form of at least one constitutent of the
frozen piercing implement. In one embodiment, the solvent includes
a salt solution. In one embodiment, the solvent includes an aqueous
or non-aqueous fluid.
In one embodiment, the frozen piercing implements are removed from
the mold or frame by applying at least one of mechanical energy,
electrical energy, electromagnetic energy, magnetic energy, or
thermal energy. In one emobodiment, the frozen piercing implements
are removed from the mold or frame by applying one or more of a
vibrational force, torisonal force, compressive force, rarefaction
force, or contact force (including but not limited to a collision
force, such as an elastic collision or inelastic collision). In one
embodiment, the frame or mold includes a portion with at least one
energy producing or energy conducting component. In one embodiment,
the frame or mold is stacked together in a sandwich configuration
with at least one energy producing or energy conducting component
layer in between. In one embodiment, the energy producing or energy
conducting component includes a mesh electrical mat. See, for
example, U.S. Pat. No. 7,241,979, which is incorporated herein by
reference. In one embodiment, the mold or frame includes at least
one thermoregulator or other regulator. In one embodiment, the
energy producing or energy conducting component includes at least
one thermoregulator or other regulator.
In one embodiment, the frozen particle compositions, or frozen
piercing implements are fabricated by vapor condensation or
deposition onto a support surface, including but not limited to a
cryo-surface. See, for example, Hallbrucker et al, J. Phys. Chem.
93, pp. 4986-4990 (1989); and Mayer and Pletzer, J. Chem. Phys. 80
(6) pp. 2939-2952, each of which is incorporated herein by
reference. In one embodiment, the cryo-surface includes a cryoplate
or cryowire. For example, samples of amorphous solid water are
prepared by depositing water vapors from a reservoir of hydrogen
oxide held at room temperature through a fine metering valve and a
tume into a high vacuum system, where the hydrogen oxide is
condensed on a copper structure precooled to approximately 77K
(approximately -196.degree. C.). Id. In one embodiment, a baffle is
used above the entrance tube to avoid supersonic flow of the
hydrogen oxide vapor, which can cause rough surfacing of the
particles. Id. In one embodiment, a supersonic flow of the hydrogen
oxide vapor is desired, and no baffle is used. For example, in the
absence of a baffle, supersonic expansion by adiabatic cooling
gives a frozen amorphous solid particle with pores or voids, which
allow for other fluids, including but not limited to inert gases
(e.g., oxygen, nitrogen, or helium), to be adsorbed or enclosed
within the frozen particle composition. Id. For example, the
microporous structure allows amorphous ice a large ability to trap
gases within the solid frozen particle composition. See, for
example, Westley, et al., J. Chem. Phys. vol. 108, pp. 3321-3326
(1998), which is incorporated herein by reference.
In one embodiment, a method of making a frozen particle
composition, including a frozen piercing implement, includes a
standard refrigeration mechanism for cooling or supercooling at
least one fluid constituent. For example, one form of standard
refrigeration for freezing fluids includes a helix of stacked pipe
coils surrounding and supporting a central support member having a
hollow core, covered by a sleeve member. See, for example, U.S.
Pat. No. 4,351,157, which is incorporated herein by reference.
In one embodiment, the pipe helix includes an evaporator and
includes a metal, such as copper. Id. In one embodiment, the hollow
central support member includes an insulating material, such as
foam or plastic. Id. In one embodiment, the sleeve member includes
a highly thermally conductive material, such as aluminum. Id. In
one embodiment, the sleeve member is in substantial surface contact
with the outer surface of the pipe helix. Id. Other standard
refrigeration components are disposed in housing and can include at
least one of a compressor, expansion valve, filtering and drying
element liquid receiving means, condenser, or condenser fan. Id. In
one embodiment, the refrigeration means utilizes standard
refrigerating fluids, such as FREON.RTM.. Id. In one embodiment,
the helix of coils surrounded by a thermally conductive metal in
substantial surface contact with the stack of coils results in
formation of a frozen layer on the outer surface of the thermally
conductive sleeve, even in environments not otherwise conducive to
formation of frozen compositions, or frozen piercing implements.
Id. This frozen layer on the outer surface of the thermally
conductive sleeve can be etched, cut, or otherwise fabricated into
frozen particle compositions, or frozen piercing implements.
In one embodiment, the frozen composition utilized for fabricating
frozen particle compositions, or frozen piercing implements is
exposed to conditions for a time sufficient to at least partially
thaw the frozen composition. Subsequently, the at least partially
thawed composition is frozen solid again. In one embodiment, the
freeze-thaw-freeze alters the surface of the frozen composition.
See, for example, U.S. Pat. No. 1,891,230, which is incorporated
herein by reference. In one embodiment, the altered surface
includes a hardened outer surface, or "crust." Id. In one
embodiment, the frozen composition is embossed or stamped in order
to fabricate at least one frozen particle composition, or frozen
piercing implement. Id. In one embodiment, the frozen composition
undergoes at least one thaw or partial thaw while contacting the
embossing or stamping mold or equipment. In one embodiment, the
frozen composition is exposed to at least one additional freezing
temperature while contacting the embossing or stamping mold or
equipment. In one embodiment, the embossing or stamping mold or
other equipment is heated while contacting the frozen composition.
In one embodiment, the frozen composition is positioned on a
surface, and the embossing or stamping occurs from one side or one
direction. In one embodiment, the frozen composition is positioned
so as to "thread" through an embossing or stamping device, wherein
the embossing or stamping occurs from more than one side or more
than one direction. In one embodiment, the frozen particle
compositions, or frozen piercing implements are collected
subsequent to the embossing or stamping. Id. In one embodiment, the
frozen particle compositions, or frozen piercing implements, are
collected into a cryofluid or refrigerant. In one embodiment, the
frozen particle compositions, or frozen piercing implements, are
collected in at least one compartment. In one embodiment, the at
least one compartment includes at least one refrigerant or
cryogenic fluid. In one embodiment, the at least one compartment
includes at least one of liquid nitrogen, liquid Freon.RTM., liquid
oxygen, or supercooled fluid.
In one embodiment, the frozen piercing implement includes a
sidewall, or shaft, as shown in FIGS. 121, 126, and others. In one
embodiment, the angle of the sidewall, or angle of the piercing
implement tip, includes at least one of at least approximately
0.degree., approximately 5.degree., approximately 10.degree.,
approximately 20.degree., approximately 30.degree., approximately
40.degree., approximately 45.degree., approximately 50.degree.,
approximately 60.degree., approximately 70.degree., approximately
80.degree., approximately 90.degree., or any value therebetween or
greater.
In one embodiment, an apparatus is used for preparing frozen
hydrogen oxide particle compositions. See, for example, Mayer and
Pletzer, Ibid. For example, in one embodiment, frozen particle
compositions are prepared by admitting hydrogen oxide vapor from a
reservoir of liquid hydrogen oxide at room temperature, through a
needle valve and a nozzle into a high vacuum system, condensing the
vapor on a support structure precooled to approximately 77 K
(approximately -196.degree. C.). Id. In the apparatus, vapor is
condensed directly in the sealed bottom part of a 10 mm diameter
glass tube. Id.
In one embodiment, the frozen particles are prepared in situ, and
devitrification is conducted in the presence of gas or in vacuo.
Id. In one embodiment, the apparatus allows for observation of the
devitrification either in vacuo without any prior contact of the
hydrogen oxide with inert gas, or in the presence of various inert
noncondensible gases (99.99% purity). Id.
In one embodiment, the apparatus includes copper tubes of various
lengths (with 13 and 4 mm inner diameter) used as nozzles. Id.
Various nozzle shapes can be used. Id. Additionally, the apparatus
includes an optional baffle or deflector, such as a copper plate
held at room temperature between the neozzle exit and the
cryoplate. Id. In one embodiment, an oil diffusion pump with 130
l/s pumping capacity is used, with a base pressure of 10.sup.-5 and
10.sup.-6 mbar during condensation. Id. The hydrogen oxide
condensates can be transferred from the copper cryoplate into
liquid nitrogen, and subsequently with a liquid nitrogen cooled
spoon to an analytical instrument, or other location. Id.
In one embodiment, frozen hydrogen oxide particle compostions were
prepared by condensation of gas evaporating from a surface of ice
Ih at approximately 210 K (approximately -63.degree. C.), with a
chloroform slush bath. Id. In one embodiment, the coolfinger
apparatus is inserted into a large tube with a sealed flat bottom
for the crystalline ice reservoir, without the need for the nozzle.
Id.
In one embodiment, differential thermal analysis of a sample of the
resulting frozen hydrogen oxide particle compositions is conducted
are conducted using standard techniques. Id. In one embodiment, the
samples are heated from between approximately 83 K (approximately
-190.degree. C.) and approximately 90 K (approximately -183.degree.
C.) with 6 degrees/minute as a heating rate. Id.
In one embodiment, frozen particle compositions including at least,
for example, methanol, toluene, butanol, ethanol, pentanol, or
isopropylbenzene are prepared in the same manner, utilizing the
apparatus as depicted in published studies. Id.
In one embodiment, the size, morphology, or porosity can be
modulated by altering the temperature, pressure, or angle of
incidence for which the vapor is deposited. See, for example,
Hallbrucker et al, Ibid. In one embodiment, including at least one
second fluid with the frozen particles during an annealing process,
results in incorporation of the at least one second fluid in the
frozen particle compositions, or frozen piercing implements. Id.
For example, on heating amorphous solid water from approximately
77K (approximately -196.degree. C.) a decrease in surface area
occurs and sintering proceeds as pores close and become isolated.
Id. In one embodiment, for example, the annealing process is
carried out in the presence of nitrogen or other gases, and the
adsorbed gases become enclosed in the pores during sintering. Id.
The gas cannot be removed by pumping at low temperatures, but is
gradually given off during the warming of the sample up to
approximately 273 K (approximately 0.degree. C.). Id. Accordingly,
the frozen particle compositions, or frozen piercing implements
that include at least one second fluid generally retain a larger
size than the frozen particle compositions, or frozen piercing
implements that do not contain an additional fluid. Id.
In one embodiment, at least one of the vapor deposition process or
the annealing process is at least partially conducted in a vacuum,
which generates frozen particle compositions, or frozen piercing
implements at least substantially without other gases present in
the frozen particle compositions, or frozen piercing implements.
Id.
In one embodiment, ice Ic is formed by heating amorphous solid
water or hyperquenched glassy water to approximately 150 K to
approximately 162 K (approximately -123.degree. C. to approximately
-111.degree. C.). Id. In one embodiment, a reversible glass to
liquid transition occurs with an onset temperature of approximately
136 K+/-1 K (approximately -137.degree. C. +/-1.degree. C.) with a
range of transition of approximately 14 K, or 14.degree. C., and
the increase in heat capacity is approximately 1.9 +/-0.2 J/Kmol.
Id. In one embodiment, the heat of crystallization of amorphous
solid water to ice Ic is approximately -1.29+/-0.01 kJ/mol. Id.
In one embodiment, for example, published studies have shown that
hydrogen oxide prepared at a temperature lower than approximately
140 K (approximately -133.degree. C.) include amorphous granules in
submicrometer size. See, for example, Boxe et al., Abstract, J
Colloid and Interface Sci. Vol. 309 pp. 412-418 (2007), which is
incorporated by reference herein. In one embodiment, for example,
at near 180-200K (approximately -93.degree. C.-approximately
-73.degree. C.), solid hydrogen oxide produces hexagonal or cubic
granules or particles in micrometer size or smaller. Id. Ice
particle size can be increased, for example, by brief annealing at
even warmer temperatures to sizes approaching approximately 10
.mu.m. Id. In one embodiment, the particle size or phase is
monitored or controlled. For example, environmental scanning
electron microscopy can be used to assess particle size and phase
of particles that develop from the vapor deposition process. Id. In
one embodiment, the specific surface area of particles can be
determined from BET (Brunauer, Emmett, and Teller) analysis of gas
adsorption isotherms, as well as other methods. Id. In one
embodiment, the BET analysis includes gas adsorption of isotherms
in the temperature range from approximately 83.5 to 261 K
(approximately -190.degree. C. to -12.degree. C.). Id. As indicated
in published studies, the specific surface area of particles
generated by vapor deposition were approximately 102 m.sup.2/g at
approximately 83.5K (approximately -190.degree. C.) to
approximately 0.87 m.sup.2/g at approximately 150K (approximately
-123.degree. C.), indicating that a transition from amorphous to
crystalline form of hydrogen oxide occurs at approximately 150K
(approximately -123.degree. C.).
In one embodiment, frozen particle compositions, or frozen piercing
implements are prepared in a cryopumped ultra-high vacuum chamber
capable of reaching a base pressure of approximately
1.times.10.sup.-10 Torr, as published by Westley et al Ibid. In one
embodiment, ice films are grown on an optically flat gold electrode
of a quartz crystal resonator for a microbalance. Id. For example,
the crystal holder is attached to a closed-cycle refrigerator and
surrounded by two heat shields at approximately 30 K (approximately
-243.degree. C.) and 60 K (approximately -213.degree. C.),
respectively. Id. The films are formed by flowing degassed
high-purity apor through an array of 0.5 mm long, 50 .mu.m diameter
capillaries approximately perpendicular to the gold surface. Id.
Films of thickness between approximately 0.01 .mu.m and
approximately 3 .mu.m were grown at rates in the range of 0.6
nm/minute to 2 nm/minute at support structure temperatures of
approximately 30 K (approximately -243.degree. C.) to 140 K
(approximately -133.degree. C.). Id. In one embodiment, morphology,
density and porosity of frozen particle compositions can be varied
according to one or more of the constitution of the support
structure, the direction of the fluid flow, or the vacuum
conditions. Id.
In one embodiment, varying the angular distribution of the incident
vapor molecules to the support structure controls the morphology or
porosity of the frozen particle compositions. See, for example,
Stevenson, et al., Science vol. 283, pp. 1505-1507 (1999). For
example, in one embodiment, vapor deposited on a support structure
by collimated, effusive hydrogen oxide beams have a region of
uniform thickness (umbra) surrounded by a region of decreasing
thickness (penumbra), whereas vapor deposited on a support
structure by ambient vapor are uniform across the entire sample, as
verified by Auger electron spectroscopy and temperature-programmed
desportion. Id. In one embodiment, the deposition rates of hydrogen
oxide vapor on a support structure include 0.02 to 0.12 bilayer per
second, where 1 bilayer is approximately equal to
1.1.times.10.sup.15 molecules per square centimeter). Id. In one
embodiment, adsorption of gas (e.g., oxygen, argon, or nitrogen) by
amorphous solid water frozen particle compositions, or frozen
piercing implements grown with a deposition angle less than or
equal to approximately 20.degree. is similar to the adsorption by a
crystalline ice film. Id. In one embodiment, adsorption of gas by
amorphous solid water frozen particle compositions, or frozen
piercing implements grown with a deposition angle greater than
approximately 30.degree. C. increases markedly, reaching a maximum
when the angle of deposition is approximately equal to 70.degree.
C. Id. At the maximum gas adsorption, amorphous solid water adsorbs
more than 20 times the amount of gas adsorbed by a crystalline ice
film. Id.
In on embodiment, morphology, density, or porosity can be
controlled by the angle of incidence of the vapor particles
contacting the support structure, as illustrated by ballistic
deposition. Id. For example, the formation of porous, columnar
films by oblique deposition has been demonstrated to be
controllable for a variety for structurally-stable, high-melting
point solids, including but not limited to metals, oxides, or
semiconductors. Id. Accordingly, for preparation of frozen particle
compositions, or frozen piercing implements, morphology, density,
or porosity can be controlled by angle of vapor deposition from
approximately straight-line trajectories that yield less porous
surfaces to an increasing or decreasing angle of deposition, that
result in films of varying thicknesses and growth rates, providing
a shadow of particular background regions of the support structure.
Id.
In one embodiment, frozen particle compositions, or frozen piercing
implements are prepared by controlling the pressure and temperature
of hydrogen oxide, or other particle composition constitutent,
introduced as a liquid, gas, or solid. In one embodiment, ice Ic is
prepared by hyperquenching pure hydrogen oxide droplets onto a cold
substrate (below approximately 190 K, or approximately -83.degree.
C.), as described herein.
In one embodiment, ice Ic is prepared by freezing hydrogen oxide
clusters (approximately 6.6-5.5 nm) at 200 K (approximately
-73.degree. C.), or by homogenous freezing at approximately 235 K
(approximately -38.degree. C.) of an emulsion of hydrogen oxide
droplets in an oil matrix. See, for example, Murray and Bertram,
Phys. Chem. Chem. Phys. vol. 8, pp. 186-192 (2006), which is herein
incorporated by reference.
In one embodiment, emulsions of pure hydrogen oxide droplets are
prepared by mixing distilled, filtered hydrogen oxide with an oil
phase in a proportion of approximately 30-40% water in oil (by
mass). Id. In one embodiment, the oil phase includes approximately
10% surfactant (such as lanolin) in hydrocarbon oil (such as
paraffin oil). Id. In one embodiment, emulsions are cooled to
approximately 173 K (or approximately -100.degree. C.) at a rate of
approximately 10 K (or degrees Celsius)/minute, while monitoring
ice reflection (with the diffraction angle of approximately
24.degree. or approximately)40.degree.. Id. In one embodiment, the
freezing range of pure hydrogen oxide is between approximately
237.5 +/-1 K and 230.4 +/-1 K (approximately -35.6.degree. C.
+/-1.degree. C. and -42.75.degree. C. +/-1.degree. C.), which
indicates that neither the oil nor surfactant significantly alters
the nucleation process of the freezing droplets. Id.
In one embodiment, the mixture is agitated for 5-10 minutes or
until the droplets are of the desired size, which can be determined
by standard techniques, such as optical microscopy. Id. Droplet
size can be varied by adjusting the agitation time, and droplet
size allows for selection of ice structure with nearly all frozen
particles existing as ice Ic at a volume median diameter of
approximately 5.6 .mu.m. Id. Ice Ic is stable in the emulsions, as
in other contexts, below approximately 240 K (approximately
-33.degree. C.), when it undergoes a solid state transformation to
ice Ih (unless formed in nanoporous material). Id. In one
embodiment, selecting for ice Ic during crystallization of hydrogen
oxide can be conducted by keeping the rate of heat dissipation
greater than the rate of heat production by the crystallization
process. Id.
As with other methods of preparing frozen particle compositions, or
frozen piercing implements, the structures of the frozen particle
compositions, or frozen piercing implements prepared in this manner
can be analyzed by standard techniques, including for example,
x-ray diffraction. Id.
In one embodiment, the frozen particle compositions, or frozen
piercing implements are made by contacting at least one sterile
first fluid droplet with at least one surface. In one embodiment,
the at least one surface includes at least one hydrophobic, super
hydrophobic, or omniphobic surface. In one embodiment, the at least
one sterile first fluid droplet changes in density while the fluid
solidifies or freezes. In one embodiment, the at least one droplet
is exposed to at least one force. In one embodiment, the at least
one force includes one or more of gravitational force, centrifugal
force, centripetal force, magnetic force, electromagnetic force,
capillary action, surface tension, expansion force, pneumatic
force, air pressure, fluid pressure, electromotive force, or
electrical force. In one embodiment, as the droplet density
changes, at least one frozen projection is formed. In one
embodiment, the at least one frozen projection includes a hollow
tube through which supercooled fluid passes and freezes at the tip,
thereby growing the at least one projection. In one embodiment, the
at least one frozen projection forms by way of reverse sublimation.
In one embodiment, the at least one frozen projection forms in
accordance with the Bally-Dorsey model. See, for example,
Blanchard, J. Meterology, vol. 8, pp. 268-269 (1951), each of which
is incorporated herein by reference. In one embodiment, the at
least one frozen projection forms by way of crystallization.
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by pulling a roll or tube of
the composition while increasing the temperature or pressure on the
composition in order to increase the viscosity. See, for example,
Purves, Biophys. J. vol. 29, pp. 523-530 (1980), which is
incorporated herein by reference. For particular compositions that
may have low viscosity, or low tensile strength, at least one agent
can be added to increase these characteristics. For example, one or
more of a polymer, wax, fat, carbohydrate, protein, gelatin, or
other agent can be added to the fluid composition, for example,
hydrogen oxide or another constituent in order to increase tensile
strength.
In one embodiment, the frozen particle compositions, or frozen
piercing implements are generated by first combining the
constituents, including any additional agents (such as therapeutic
agents, reinforcement agents, abrasives, explosive materials,
adhesive agents, biological remodeling agents, or other agents)
under appropriate conditions. Next, the combined constituents are
freeze dried. As indicated herein, in one embodiment, the frozen
particle compositions, or frozen piercing implements include but
are not limited to mixtures, solutions, suspensions, dispersions,
gels, or other combinations.
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by spinning. In one embodiment,
the frozen particle compositions, or frozen piercing implements,
are fabricated by melt-spinning, dry spinning, gel spinning,
extrusion spinning, electro-spinning, direct spinning, or wet
spinning. In one embodiment, gel spinning is conducted with DMSO as
a solvent, or as part of the spun composition. See, for example,
Fukae et al., Abstract, Polymer Comm., vol. 46, pp. 11193-11194
(2005), which is herein incorporated by reference.
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by embossing or casting. In one
embodiment, molds for embossing or casting are machined, milled,
drilled, or pressed according to standard techniques. In addition,
as described herein, standard lithographic methods can be used,
followed by electroplating or wet/dry etching for preparing molds.
In one embodiment, isothermal embossing is utilized, in which the
constituents and the mold are heated above the glass transition
temperature, and then pressed against the mold. In one embodiment,
non-isothermal embossing is utilized, in which the mold alone is
heated and pressed. As described herein, in certain cases where the
glass transition temperature for a particular frozen particle
composition , or frozen piercing implements is low, the articles
used to make the frozen particle compositions, or frozen piercing
implements are also kept at a low temperature, and heating any
particular article occurs relative to the glass transition
temperature.
In one embodiment, a frozen piercing implement or frozen piercing
implement device is embossed in a frozen composition. A mold
fabricated from a pre-existing microneedle array, for example, can
be utilized. The micromold is coated with at least one constitutent
by, for example, vapor deposition, and the frozen piercing
implements are etched from the non-embossed side until the embossed
cavity is exposed. See, for example, U.S. Pat. No. 7,344,499, which
is incorporated herein by reference. Next, at least one constituent
is deposited on the embossed side and sidewalls, but not on the
non-embossed side. Id. The micromold is then removed to form the
frozen piercing implement(s).
In one embodiment, the frozen particle compositions, or frozen
piercing implements, are fabricated by injection molding or
rapid-injection molding. In one embodiment, for example, the
combined constituents are injected into a cavity or die, then
cooled under conditions sufficient to solidify the constituents. In
one embodiment, the composition solidifies in a short amount of
time. In one embodiment, the composition solidifies in a longer
period of time. In certain instances, depending on the constitution
of a particular composition, the time from injection to
solidification can be adjusted for specific desired results. See,
for example, U.S. Pat. No. 6,572,796, which is incorporated herein
by reference.
In one embodiment, the frozen particle compositions, or frozen
piercing implements are made by calendering. In certain instances,
the constituents are combined and placed under conditions
sufficient to solidify the combined constituents (including but not
limited to high pressure or lower temperature) before or during
calendering the combined constituents into a sheet or layer on a
base. Various constituents can be layered together in multiple
layers, or can be combined in a single layer. The frozen particles
can then be further processed to attain the desired size, shape,
etc. by cutting, etching, embossing, or similar technique.
In one embodiment, the devices associated with or including at
least one frozen piercing implement, including but not limited to
frozen piercing implement array devices, fluidic devices, or
injection devices, are at least partially fabricated by
micromachining techniques. In one embodiment, surface
micromachining, bulk micromachining, or a combination thereof is
used.
In one embodiment, the frozen piercing implements are made by
providing at least one fluid composition, and utilizing at least
one force configured to induce at least one projection in the at
least one fluid composition. In one embodiment, the at least one
force includes at least one of: gravitational force, centrifugal
force, centripetal force, magnetic force, electromagnetic force,
capillary action, surface tension, expansion force, pneumatic
force, air pressure, fluid pressure, electromotive force, or
electrical force, or the like.
In general, the volumetric flow rate Q forming icicle-like piercing
implements is on the order of tens of milliliters per hour
(approximately 0.01 cm.sup.3/second), and icicle radii are
generally in the range of approximately 1-10 cm. See, for example,
Short et al., Phys. Fluids, vol. 18, pp. 083101-1-5, (2006), which
is incorporated herein by reference. As such, a cylindrical icicle
of radius r, has an aqueous film flow of thickness h, and since h
is smaller than r over nearly the entire icicle surface, the
velocity profile in the layer may be determined as that flowing on
a flat surface. Id. If y is a coordinate normal (or approximately
so) to the surface and .theta. is the angle that the tangent vector
.tau. makes with respect to the horizontal, then the Stokes
equation for gravity-driven flow is v.sub.wd.sup.2u/dy.sup.2=sin
.theta., where g is the gravitational acceleration and v.sub.w=0.01
cm.sup.2/second is the kinematic viscosity of hydrogen oxide.
Id.
Additionally, piercing implements can be made from a single drop or
droplet of at least one fluid composition by applying a scaling
factor or the aspect ratio. Id. For example, dimensionless profiles
can be constructed for a desired form by applying the formula for
the "ideal icicle shape," in accordance with naturally occurring
icicle shapes, which is .rho.=4/3 (.zeta..sup.1/2+2)
.zeta..sup.1/2-1. Id. Likewise, for example, evaluating the
asymptotic form at some point on the surface (.rho.*, .zeta.*)
where the aspect ratio (length/width) is A=.zeta.*/.rho.*, and the
shape can be written as
.zeta./.zeta.*.apprxeq.(.rho./.rho.*).sup.4/3, a universal,
self-similar form, regardless of the droplet size. Id. In this
regard, it is possible to predict or compute parameters for a
frozen piercing implement based on the natural formation of
icicles.
In one embodiment, acoustic force is utilized to induce at least
one projection from at least one fluid composition. For example,
the shape of a drop or bubble can be distorted, and internal flow
manipulated, by shifting the resonant frequencies of natural shape
oscillations.
In one embodiment, the frozen particle compositions are made with
at least one compound that has been sterilized (e.g., by
filtration, by ultraviolet light, or other method), degassed, or
deionized.
In one embodiment, at least one first fluid composition is
contacted with at least one second fluid for a time and condition
sufficient to form one or more frozen particle compositions, or
frozen piercing implements as described herein.
In one embodiment, at least one agent (e.g., a reinforcement agent)
is utilized to freeze with one or more components, or substances.
In one embodiment, the at least one agent is substantially a solid,
and at least one substance or component is substantially a liquid.
The combination is then frozen, and frozen particle compositions
are generated as described herein.
In one embodiment, one or more frozen particle compositions or
frozen piercing implements are extruded by way of a die, or
molding. In one embodiment, the constituents are combined during
the extrusion process. In one embodiment, a spinneret is utilized
for extrusion of frozen particle compositions or frozen piercing
implements. In certain instances, the compositions are extruded in
a semi-solid state, and then further solidified. In one embodiment,
different dies or extrusion plates are used with the spinneret in
order to form particular cross-sectional shapes (e.g., round,
trilobal, pentagonal, octagonal, etc.). In one embodiment, a
configuration can be used that resists bending of the extrudate,
particularly when the extrudate is composed of multiple
constituents. See, for example, PCT Publication No. WO/2000/070131,
which is incorporated herein by reference.
In one embodiment, one or more frozen particle compositions, or
frozen piercing implements are generated with assistance of at
least one refrigerant or cryogen, including but not limited to
liquid nitrogen, liquid carbon dioxide, etc.
In one embodiment, at least one agent (e.g., a reinforcement agent)
is utilized to crystallize one or more components or substances.
The crystallization is frozen, and frozen particle compositions, or
frozen piercing implements are generated as described herein.
In one embodiment, the size of at least one frozen particle
composition is measured. In one embodiment, the size of at least
one frozen particle composition is measured according to particle
size distribution. In one embodiment, the frozen particle
composition size may be measured by, for example, sieve analysis,
optical counting methods, electron microscopy, disc centrifugation,
electrozone sensing, dynamic light scattering, electroresistance
counting methods, scanning tunneling microscopy, atomic force
microscopy, sedimentation techniques, laser diffraction methods,
acoustic spectroscopy, ultrasound attenuation spectroscopy, and the
like. In one embodiment, the size distributions are measured, for
example, by utilizing an electrical mobility sizing technique in
accordance with the National Institute of Standards and Technology
Standard Reference Material Particles. See, for example,
Application Note SMPS-003, on the worldwide web at tsi.com; the
subject matter of which is herein incorporated by reference. In one
embodiment, the size distribution of a particular lot of frozen
particle compositions, or frozen piercing implements is measured by
utilizing, for example, a Scanning Mobility Particle Sizer.TM.
(SMPS) spectrometer. Id. For example, the SMPS spectrometer
utilizes a differential mobility analyzer to size classify the
particle stream and a condensation particle counter to determine
the concentration at each size. Id. The differential mobility
analyzer utilizes the fact that a particles' electrical mobility
(Z.sub.p, or the ability of a charged particle to move in an
electric field) is roughly inversely proportional to particle
diameter. Id. Additionally, size distribution measurements can be
made in real-time with the SMPS spectrometer. Id.
In one embodiment, size distributions of electrospray droplets from
a Taylor cone are directly measured by using a freezing method and
a transmission electron microscope image processing. See, for
example, Ki Ku, et al., Abstract, J. Aerosol Sci., vol. 32, no. 12,
pp. 1459-1477 (2001), which is incorporated herein by
reference.
In one embodiment, one or more methods, devices, or systems
described herein include delivering or administering one or more
frozen particle compositions, or frozen piercing implements by high
velocity impact. In one embodiment, the one or more devices that
utilize high velocity impact delivery provide at least one of
localized delivery, targeted delivery, sustained delivery,
modulated delivery, feedback controlled delivery. In some
instances, an example of a device that can be used for
administering one or more of the compositions described herein
includes a handheld device, such as a wand, pen, baton, hose,
sprayer, spigot, gun (e.g., particle or pellet gun), or other
device. In certain instances, the device is at least part of a
built-in delivery device, such as can be included in a wall, an
overhead device, a corral, a gate, or a device that includes a
cavity into which a subject can be placed for administration or
delivery of at least one composition described herein. In certain
instances, the device has robotic action. In any of these
instances, the device can be remotely controlled, for example, by a
human, computer system, or computer program. In one embodiment, the
device can be built in, for example, in a room (e.g., hospital
room, surgical room, greenhouse, food or beverage facility, outdoor
or indoor arena or stadium, home, institutions, etc.).
In one embodiment, a method for making one or more frozen particle
compositions, or frozen piercing implements includes passing one or
more droplets of at least one fluid composition through a
compartment that is configured to provide conditions for a time
sufficient to freeze the one or more droplets; wherein the
compartment includes at least one hydrophobic surface and wherein
the at least one fluid composition includes at least one fluid and
at least one agent. In one embodiment, the at least one hydrophobic
surface is reversible to at least one hydrophilic surface. In one
embodiment, the reversible hydrophobic surface includes at least
one vanadium oxide nanostructured film. See, for example, Lim et
al, J. Am. Chem. Soc., Abstract, vol. 129, pp. 4128-4129 (2007),
which is incorporated herein by reference. For example, fabrication
of a roselike nanostructured vanadium oxide (V.sub.2O.sub.5) film
with photoinduced surface wettability switching can be conducted by
drop-casting a suspension of vanadium oxide particles. Id. In one
embodiment, the suspension of vanadium oxide particles is
synthesized with the sol-gel method. Id. In one embodiment,
alkylamine is added to the vanadium oxide, in such a manner that
alkyl chains are intercalated between the vanadium oxide layers.
Id. The surface is tunable, for example, by exposing the surface to
ultraviolet light, the surface becomes superhydrophilic, while
exposure to darkness renders the surface superhydrophobic. Id.
In one embodiment, a method for administering at least one frozen
piercing implement to at least one substrate comprises contacting
at least one substrate with at least one frozen piercing
implement.
In one embodiment, administering the at least one frozen piercing
implement to at least one substrate includes accelerating,
propelling, pushing, pulling, or ejecting the at least one frozen
piercing implement toward the at least one substrate. In one
embodiment, administering the at least one frozen piercing
implement to at least one substrate includes drilling or
administering with a screw-type action. In one embodiment,
administering the at least one frozen piercing implement to at
least one substrate includes accelerating, propelling, pushing,
pulling, or ejecting the at least one substrate toward the at least
one frozen piercing implement. In one embodiment, administering the
at least one frozen piercing implement to at least one substrate
includes propelling, ejecting, pushing, pulling, drilling, or
accelerating the at least one frozen piercing implement toward the
at least one substrate with at least one of a predetermined angle,
predetermined velocity, predetermined force, predetermined
substrate stress, predetermined rate of administration,
predetermined depth, predetermined location, predetermined time
sequence, or predetermined spatial pattern. In one embodiment, the
method further comprises varying the rate, velocity, force, or
angle at which the at least one frozen piercing implement is
administered to the at least one substrate.
In one embodiment, administering the at least one frozen piercing
implement to at least one substrate includes propelling, ejecting,
pushing, pulling, drilling, or accelerating a plurality of frozen
piercing implements toward the at least one substrate. In one
embodiment, propelling, ejecting, pushing, pulling, drilling, or
accelerating the plurality of frozen piercing implements toward the
at least one substrate includes propelling, ejecting, or
accelerating the plurality of frozen piercing implements at one or
more of a predetermined angle, predetermined velocity,
predetermined rate of administration, predetermined spatial
pattern, predetermined location, predetermined time sequence,
predetermined force, predetermined substrate stress, or
predetermined depth. In one embodiment, two or more of the
plurality of frozen piercing implements each includes at least one
agent that physically or chemically bind upon administration. In
one embodiment, administering the at least one frozen piercing
implement occurs prior to, during, or subsequent to surgery.
In one embodiment, the method further comprises varying the rate,
velocity, force, or angle at which the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device is administered to the at least one substrate. In
one embodiment, administering the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device occurs prior to, during, or subsequent to
surgery.
In one embodiment, the method further comprises administering to
the at least one substrate at least one article including an
optical, photonic, or electronic article. In one embodiment, the at
least one article is configured to communicate with at least one
computer system. In one embodiment, the at least one article is
configured to monitor at least one characteristic of the at least
one substrate. In one embodiment, the at least one substrate
includes at least one biological cell or tissue, and the at least
one characteristic of the at least one substrate includes one or
more of: tissue formation, tissue growth, cell proliferation, cell
differentiation, nuclear division, apoptosis, dissolution,
deterioration, biochemical function of at least one cell,
biochemical function of at least one tissue, biochemical function
of at least one organ, structural integrity, structural function,
immunological reaction, or durability of the at least one
biological tissue.
In one embodiment, the at least one article includes at least one
temperature-sensitive substance. In one embodiment, the at least
one article is intermixed with the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment, the at least one article is
located in the at least one frozen piercing implement. In one
embodiment, the at least one article includes at least one
electronic identification device. In one embodiment, the at least
one electronic identification device includes at least one radio
frequency identification device.
In one embodiment, the at least one article includes at least one
radioactive, luminescent, colorimetric or odorous substance. In one
embodiment, the at least one article is configured to sense at
least one change in temperature. In one embodiment, the at least
one article includes at least one of a diamagnetic particle,
ferromagnetic particle, paramagnetic particle, super paramagnetic
contrast agent, particle with altered isotope, or other magnetic
particle.
In one embodiment, the method further comprises adjusting the
temperature of the at least one substrate prior to, during, or
subsequent to administering the at least one frozen piercing
implement to at least approximately 37.degree. C., approximately
36.degree. C., approximately 35.degree. C., approximately
34.degree. C., approximately 33.degree. C., approximately
32.degree. C., approximately 31.degree. C., approximately
30.degree. C., approximately 29.degree. C., approximately
28.degree. C., approximately 27.degree. C., approximately
26.degree. C., approximately 25.degree. C., approximately
24.degree. C., approximately 23.degree. C., approximately
22.degree. C., approximately 21.degree. C., approximately
20.degree. C., approximately 19.degree. C., approximately
18.degree. C., approximately 17.degree. C., approximately
16.degree. C., approximately 15.degree. C., approximately
14.degree. C., approximately 13.degree. C., approximately
12.degree. C., approximately 11.degree. C., approximately
10.degree. C., approximately 9.degree. C., approximately 8.degree.
C., approximately 7.degree. C., approximately 6.degree. C.,
approximately 5.degree. C., approximately 4.degree. C.,
approximately 3.degree. C., approximately 2.degree. C.,
approximately 1.degree. C., approximately 0.degree. C., or any
temperature less than or therebetween.
In one embodiment, contacting at least one substrate includes at
least one of cutting, stitching, cauterizing, freezing,
perforating, penetrating, ablating, or abrading at least a part of
the surface of the at least one substrate. In one embodiment,
administering the at least one substrate occurs in conjunction with
cryosurgery, cryotherapy, or mesotherapy.
In one embodiment, the method further comprises sensing or
extracting at least one material from the at least one substrate.
Various non-limiting examples of materials that are capable of
being sensed or extracted from at least one substrate are provided
herein.
In one embodiment, contacting at least one substrate affects one or
more of electrical resistance of the at least one substrate, or
permeability of the at least one substrate. In one embodiment, the
method further comprises withdrawing the at least one frozen
piercing implement from the at least one substrate.
In one embodiment, a method of vaccinating a subject includes
administering to a subject at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device that includes at least one vaccine. Specific
examples of compositions including frozen piercing implements
including vaccines are described herein.
In one embodiment, a method includes delivering at least one agent
to at least one substrate, wherein the agent is included as part of
a frozen piercing implement. In one embodiment, a method for
piercing at least one substrate includes piercing at least one
substrate with a frozen piercing implement including at least one
agent. Specific examples of compositions including frozen piercing
implements are described herein.
In one embodiment, a method for administering a frozen piercing
implement device that includes at least one frozen piercing
implement includes contacting the frozen piercing implement device
(e.g., an array device, fluidic device, or injection device, etc.)
with at least one substrate. In one embodiment, a method for
delivering at least one agent includes administering at least one
frozen piercing implement device to at least one substrate, wherein
at least one frozen piercing implement of the device includes at
least one agent. In one embodiment, the at least one frozen
piercing implement is coated with at least one agent. In one
embodiment, the at least one agent is encapsulated in the at least
one frozen piercing implement. In one embodiment, at least one
frozen piercing implement includes at least one conduit configured
to deliver at least one agent. In one embodiment, the at least one
frozen piercing implement array is administered to at least one
substrate prior to, during, or subsequent to administering a
trans-substrate patch or iontophoretic device. In one embodiment,
the trans-substrate patch includes a transdermal patch.
In one embodiment, at least one material is extracted from the at
least one substrate. Various non-limiting examples of materials
that are capable of being extracted from at least one substrate are
described herein. In one embodiment, the at least one material
extracted from the at least one substrate is held in at least one
compartment. In one embodiment, spring means, a cantilever, gate,
expandable balloon, rigid balloon, or other regulatory means, are
configured to cause a change in volume, and corresponding change in
internal pressure, of the compartment. For example, in one
embodiment, the compartment includes a movable, rigid top with
fixed, rigid side walls, wherein the interface between the walls
and top include a gas-tight seal (for example, by placement of a
gasket or other seal). See, for example, U.S. Pat. No. 7,344,499,
which is herein incorporated by reference.
In one embodiment, at least one material is extracted by way of an
osmotic pump. Id. In one embodiment, a volume expansion or pressure
reduction in the compartment drives the at least one material into
the compartment. In one embodiment, a Luer-Lock syringe or similar
device is used for all sizes of macro-, micro-, or
nano-implements.
In one embodiment, the at least one first compartment is configured
to hold at least one material extracted from the at least one
substrate. In one embodiment, the at least one second compartment
is configured to hold at least one agent or other substance to be
administered to the at least one substrate. In one embodiment, the
at least one first compartment and the at least one second
compartment are the same compartment, and includes at least one
mode of intaking at least one extracted material, and at least one
mode of expelling at least one agent or other substance (e.g., at
least one detection material).
In one embodiment, the at least one agent is configured to move
from the compartment to the substrate by diffusion, sublimation,
explosive force, fracturable membrane, mechanical or electrical
gate, magnetic force, or other means. In one embodiment, the at
least one agent moves from the compartment to the substrate by
means including a pump (e.g., osmotic pump), or a plunger. In one
embodiment, the compartment includes a syringe or pump connected to
the support structure.
In one embodiment, the frozen piercing implement device includes a
sealing mechanism to assist in maintaining at least one agent in
the compartment until it is ready to be delivered or mixed with the
contents of another compartment. In one embodiment, the sealing
mechanism is a fracturable barrier interposed between the
compartment and the support structure. In one embodiment, the
frozen piercing implement device includes a means for indicating
that administration of the device has been at least initiated or
completed. In one embodiment, the means for indicating includes a
color change. In one embodiment, the frozen piercing implement
device includes, for example, a rate control means, such a as a
semi-permeable membrane, that assists in regulating flow through at
least one frozen piercing implement. In one embodiment, the frozen
piercing implement device includes multiple compartments.
In one embodiment, the frozen piercing implement device including
at least one frozen piercing implement or portion thereof, includes
a closed-loop delivery system. For example, at least one agent is
delivered at the time of administration of the at least one frozen
piercing implement device to at least one substrate. Subsequently,
at least one material is extracted or collected from the at least
one substrate. In one embodiment, the at least one material is
analyzed by at least one sensor in at least one piercing
implement.
In one embodiment, the at least one material is analyzed by at
least one sensor in at least one optional compartment. In one
embodiment, a feedback, or closed-loop provides instructions to at
least one controller to dispense at least one agent to the at least
one substrate. See, for example, U.S. Pat. No. 6,256,533, which is
incorporated herein by reference.
In one embodiment, a method includes affecting electrical
resistance in the outer surface of a subject. For example,
according to published studies, piercing skin with microneedles
causes a 50-fold reduction in the skin's electrical resistance,
which is comparable to the reduction in electrical resistance by
piercing skin with a 30-gauge "macroneedle." See, for example, U.S.
Pat. No. 6,334,856, which is incorporated herein by reference.
In one embodiment, a method includes affecting the skin
permeability of a subject. For example, solid microneedles inserted
into the skin and left in place create pathways for transport
across the skin, and increase skin permeability. See, for example,
U.S. Pat. No. 7,344,499, which is incorporated herein by reference.
In another example, solid microneedles inserted into skin and then
removed increase skin permeability. Id. In another example, hollow
microneedles inserted into the skin and left in place increase skin
permeability and transport across the skin. Id.
In one embodiment, at least one detection material is utilized with
the frozen piercing implement device. In one embodiment, the at
least one detection material is located in the frozen piercing
implement. In one embodiment, the at least one detection material
is located in the at least one compartment. In one embodiment, the
at least one detection material is configured to indicate a color
change as the at least one extracted material contacts the frozen
piercing implement. In one embodiment, the at least one detection
material is configured to indicate a color change as the at least
one extracted material contacts the at least one compartment. In
one embodiment, the at least one detection material is configured
to indicate the presence of at least one extracted material.
In one embodiment, the at least one detection material is
configured to indicate the depth of administration of the frozen
piercing implement or frozen particle composition. In one
embodiment, the at least one detection material is configured to
indicate the depth of administration of at least one agent
delivered by the frozen piercing implement or frozen particle
composition.
In one embodiment, the device includes at least one nozzle, such as
a venturi nozzle, de Laval nozzle, or virtual Laval nozzle. See,
for example, U.S. Pat. Nos. 4,038,786; 4,707,951; and 5,779,523,
each of which is incorporated herein by reference.
In one embodiment, the device includes at least one amplifier to
increase the flow or passage of the one or more frozen particle
compositions, or frozen piercing implements through or out of the
device. See, for example, U.S. Pat. No. 4,398,820, which is
incorporated herein by reference. In one embodiment, the device
includes at least one injector, such as an oblique injector, that
allows for introduction of a fluid (e.g., a gas or liquid) to
assist in moving the one or more frozen particle compositions, or
frozen piercing implements through or out of the device. (See, for
example, U.S. Pat. No. 4,555,872, which is incorporated herein by
reference.)
In one embodiment, administering or delivering the at least one
frozen particle composition, or frozen piercing implement includes
at least one of accelerating, ejecting, or propelling the frozen
particle composition, or frozen piercing implement. In one
embodiment, the at least one frozen particle composition, or frozen
piercing implement is accelerated, ejected, or propelled to or at a
predetermined pressure or predetermined velocity for delivery of
the at least one frozen particle composition or frozen piercing
implement to a desired location on or in the at least one substrate
(e.g., a biological tissue). In certain instances, the at least one
frozen particle composition, or frozen piercing implement is
accelerated, ejected, or propelled at a particular pressure, angle,
or velocity. In certain instances, the at least one frozen particle
composition, or frozen piercing implement is accelerated, ejected,
or propelled at a predetermined pressure, angle, or velocity.
The angle, velocity or pressure determined for delivery of the at
least one frozen particle composition, or frozen piercing implement
can depend on certain factors, for example, including but not
limited to, size and density of the frozen particle composition, or
frozen piercing implement, content of the frozen particle
composition, or frozen piercing implement, desired effect or
outcome of administration of the frozen particle composition, or
frozen piercing implement, density of the target tissue, density of
surrounding tissue, type of tissue, architecture of the tissue, and
other factors. In certain instances, the desired angle, velocity or
pressure for accelerating, ejecting, or propelling the at least one
frozen particle composition, or frozen piercing implement described
herein will be the minimum angle, velocity or pressure needed to
achieve desired penetration of the substrate (including a
biological tissue) with the frozen particle composition, or frozen
piercing implements whether for surface abrasion, therapeutic
delivery, or other goal.
In addition to the angle and velocity of accelerating, ejecting, or
propelling the at least one composition, other factors can affect
the depth of penetration of a particular composition, including,
for example, one or more characteristics of the particular
composition (e.g., size, shape, or constitution of the frozen
particle composition, or frozen piercing implement) or one or more
characteristics of administration of the particular composition
(e.g., the quantity of frozen particle compositions, or frozen
piercing implements administered, distance between the delivery
device and the target substrate).
The means for accelerating, ejecting, or propelling the one or more
frozen particle compositions, or frozen piercing implements
described herein are non-limiting, and may include general methods
for making, formulating, and delivering the one or more frozen
particle compositions, or frozen piercing implements. For example,
the one or more frozen particle compositions, or frozen piercing
implements may be delivered to at least one substrate (such as a
biological tissue) by carrier gas under pressure, mechanical or
electrical impulse assistance, centripetal or centrifugal force, or
others, some of which are described herein. (See e.g., U.S. Pat.
No. 4,945,050 and PCT application WO 92/01802, each of which is
incorporated herein by reference). In certain instances, the one or
more frozen particle compositions, or frozen piercing implements
are made, propelled, accelerated, or ejected simultaneously. Thus,
the frozen particle compositions, or frozen piercing implements can
be made while propelled, the frozen particle compositions, or
frozen piercing implements can be made while accelerated, the
frozen particle compositions, or frozen piercing implements can be
made while ejected, or any combination thereof.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements are delivered or administered by
utilizing a carrier fluid. In one embodiment, the carrier fluid
includes a carrier gas. In one embodiment, the carrier fluid
includes a cold fluid, including a super cooled fluid. In one
embodiment, the carrier fluid includes dehumidified air. In one
embodiment, the carrier fluid includes at least one inert gas. In
one embodiment, a method for administering one or more frozen
particle compositions, or frozen piercing implements includes
controlling the density of the one or more frozen particle
compositions, or frozen piercing implements. In one embodiment, the
method further includes monitoring the temperature of at least part
of the substrate to which the one or more frozen particle
compositions, or frozen piercing implements are administered or are
intended to be administered. In one embodiment, the method includes
slowing or stopping the delivering of the one or more frozen
particle compositions, or frozen piercing implements if the
temperature of the at least part of the substrate becomes lower
than at least one preset limit. In one embodiment, the method
includes monitoring the velocity, depth of impact or penetration,
constitution one the one or more frozen particle compositions, or
frozen piercing implements, or other parameter of administration of
the one or more frozen particle compositions, or frozen piercing
implements.
In one embodiment, the frozen piercing implements include at least
one sensor located at the initial point of contact with at least
one substrate. In one embodiment, the at least one sensor monitors
pressure at the piercing implement tip.
In one embodiment, the one or more frozen particle compositions are
delivered or administered by an inkjet printer-type apparatus or
device, by a thermal bubble device, by ultrasound-mediated
transdermal drug transport, or by other device. When a voltage is
applied, an inkjet-type apparatus generates a pressure pulse by
change in shape or size of a chamber containing a fluid (or solid),
and the pressure pulse drives the contents from the chamber. In one
particular instance, a high velocity device (such as a powderject,
air guns, or slingshot type devices) is utilized for administration
of at least one frozen particle composition or frozen piercing
implement as described here.
For example, in one embodiment, at least one frozen particle
composition or frozen piercing implement is propelled by way of a
powderject system, as described by Kumar and Philip (Trop. J.
Pharm. Res., vol. 6, No. 1, pp. 633-644 (2007), which is
incorporated herein by reference). The powderject system utilizes
high-speed gas flow (such as helium) that is usually painless and
causes minimal bleeding or damage to the skin. (See also e.g., Tang
et al., Pharm. Res., vol. 19, pp. 1160-69 (2002), which is
incorporated herein by reference). As described by Kumar and
Philip, particles are contained in a cassette between two
polycarbonate membranes located at the end of a chamber (Kumar and
Philip, Trop. J. Pharm. Res., vol. 6, No. 1, pp. 633-644 (2007),
which is incorporated herein by reference). As described by Kumar
and Philip, the polycarbonate membranes are ruptured when a carrier
gas enters the chamber under high pressure, and the rapid expansion
of the gas forms a shock wave that travels down the nozzle at a
speed of approximately 600-900 m/s. Velocities of up to about 800
m/s at the nozzle exit are reported, and the momentum density of
the particles within the gas flow can be optimized for desired
depth of penetration upon delivery to a biological tissue. (Kumar
and Philip, Trop. J. Pharm. Res., vol. 6, No. 1, pp. 633-644
(2007), which is incorporated herein by reference). In the
powderject system, particle velocity is controlled by nozzle
geometry, membrane burst strength, and gas pressure. (See e.g.,
U.S. Pat. Nos. 5,630,796; and 5,699,880, which are incorporated
herein by reference).
Metered-dose transdermal sprays may also be used for delivery of at
least one frozen particle composition or frozen piercing implement,
as described herein. As described by Rathbone, et al., in one
particular example, a topical solution containing a volatile then
nonvolatile vehicle including a therapeutic agent is administered
as a single-phase solution. (See Rathbone, et al., Modified Release
of Drug Delivery Technology, NY, Marcel Dekker, Inc. vol. 126, pp.
471-619 (2004), which is incorporated herein by reference). A
finite metered-dose application of the formulation to intact skin
results in evaporation of the volatile component, leaving the
remaining nonvolatile penetration enhancer or therapeutic agent to
partition into the stratum corneum and creating a reservoir of the
therapeutic agent(s). See Rathbone, Ibid; and Kumar, et al., Trop.
J. Pharm. Res., vol. 6, pp. 633-644 (2007), each of which is
incorporated herein by reference.
In addition to these particular examples of devices that can be
utilized for administration of the compositions described herein,
the compositions can be administered in conjunction with other
delivery devices. Likewise, the compositions described herein for
abrasion of at least one biological tissue can be delivered to the
at least one tissue by any means described herein. Some such means
for delivery of the compositions described herein include, but are
not limited to, ultrasound, iontophoresis (which involves applying
an electrical potential across skin or other tissue in order to
increase penetration of ionizable agents), diffusion,
electroporation, photomechanical waves (such as by producing pulses
with Q-switched or mode-locked lasers to the skin or other tissue),
needle-free injections, electro-osmosis, artificial vesicles, laser
radiation, magnetophoresis (utilizing a diamagnetic substance for
use with a magnetic field for increased penetration of the
composition into the biological tissue), microscissuining,
controlled heat aided delivery (which involves heating the skin
prior to or during administration), tattoos, three-dimensional
holograms, or etchings.
In one embodiment, Rathbone et al. have described artificial
vesicles that mimic cell vesicles (such as TRANSFERSOMES.RTM., from
IDEA AG, Germany) can be utilized for administration of one or more
composition described herein. Artificial vesicles penetrate the
skin barrier along the transcutaneous moisture gradient and causes
"virtual" pores between the cells in an organ without affecting its
biological properties. (See, e.g., Modified Release Drug Delivery
Technology, NY, Marcel Dekker, Inc., vol. 126, pp. 471-619 (2004),
which is incorporated herein by reference). In addition, liposomes,
erythrocyte ghosts, and niosomes also serve as carriers and can be
utilized in the administration of at least one frozen particle
composition or frozen piercing implement described herein.
In one embodiment, the one or more frozen particle compositions, or
frozen piercing implements are generated by spraying a jet or mist
of the composition constituents into a low temperature environment
(solid, liquid, gas, or any combination thereof) such that the
compositions freeze and form frozen particles. In one embodiment,
streams of frozen particles are extruded at low temperatures
through fine ducts and into a low temperature environment. In one
embodiment, the one or more frozen particles are propelled through
a nozzle or other delivery apparatus. In one embodiment, the one or
more frozen particles are delivered by utilizing flash boiling or
BLEVE, or other explosion, of a cold liquid. In one particular
example, liquid nitrogen is flash boiled in order to accelerate,
eject, or propel one or more frozen particles for delivery or
administration to at least one cell, tissue, or subject. In one
embodiment, the flash boiling is induced by one or more laser
pulses (e.g., an infrared laser pulse). In one embodiment, the one
or more frozen particles are prepared, delivered, or administered
by another means.
In certain instances, it is desirable to deliver the one or more
frozen particle compositions, or frozen piercing implements to at
least one cell or tissue, or administer the one or more frozen
particle compositions, or frozen piercing implements to at least
one subject. In at least one instance, the one or more frozen
particle compositions, or frozen piercing implements include a
plurality of frozen particle compositions, or frozen piercing
implements that include two or more subsets of frozen particle
compositions, or frozen piercing implements that are delivered or
administered in sequential order. In one embodiment, the sequential
order is predetermined, based on factors relating to, for example,
the at least one cell or tissue, the at least one subject, or the
at least one frozen particle composition, or frozen piercing
implement. In one embodiment, the sequential order is determined,
for example, during the course of delivery or administration of at
least one of the one or more frozen particles or at least one
frozen particle composition, or frozen piercing implement. In one
embodiment, the sequential order is determined by a software
program. In one embodiment, the sequential order of delivery is
randomized.
In one embodiment, the sequential order includes one or more
subsets of frozen particle compositions, or frozen piercing
implements that vary in size, shape, weight, density, location of
delivery or administration, time of delivery or administration,
angle of delivery or administration, or velocity of delivery or
administration. In one embodiment, one or more subsets of frozen
particle compositions, or frozen piercing implements are delivered
or administered according to a course of treatment (e.g., at least
one subset of relatively small frozen particle compositions, or
frozen piercing implements are administered first, followed by at
least one subset of relatively larger frozen particle compositions,
or frozen piercing implements; at least one subset of frozen
particle compositions, or frozen piercing implements are
administered in a relatively fast velocity, followed by at least
one subset of frozen particle compositions, or frozen piercing
implements administered by a relatively slow velocity; at least one
subset of frozen particle compositions, or frozen piercing
implements approximately shaped as spheroids are administered
followed by at least one subset of frozen particle compositions, or
frozen piercing implements approximately shaped as bullets,
etc.).
In one embodiment, the at least one frozen particle composition, or
frozen piercing implement is propelled using a pressure set at
least about 1 psi, about 5 psi, about 10 psi, about 20 psi, about
30 psi, about 40 psi, about 50 psi, at least about 100 psi, at
least about 200 psi, at least about 300 psi, at least about 400
psi, at least about 450 psi, at least about 500 psi, at least about
600 psi, at least about 700 psi, at least about 800 psi, at least
about 900 psi, at least about 1000 psi, at least about 1100 psi, at
least about 1200 psi, at least about 1300 psi, at least about 1400
psi, at least about 1500 psi, about 2000 psi, about 2500 psi, about
3000 psi, about 3500 psi, about 4000 psi, about 5000 psi, about
6000 psi, about 7000 psi, about 8000 psi, about 9000 psi, about
10000 psi, about 20000 psi, about 30000 psi, about 40000 psi, about
50000 psi, or any value therebetween.
In one embodiment, the at least one frozen particle composition, or
frozen piercing implement is propelled at a pressure ranging from
approximately 350 psi to approximately 1000 psi. In one embodiment,
for example for penetrating the skin (particularly epidermis or
dermis), the at least one frozen particle composition, or frozen
piercing implement is propelled at a pressure of approximately 800
psi to approximately 1000 psi. See, for example, Menon et al., Skin
Pharmacol. Physiol. vol. 20, pp. 141-147 (2007), which is
incorporated herein by reference. For example, microwounds caused
by gold beads bombarding the skin did not reseal with stratum
corneum lipids after 24 hours of organ culture. Id. In one
embodiment, these microwounds allow for increased permeability of
the substrate for delivery of at least one agent.
In one embodiment, the at least one frozen particle composition, or
frozen piercing implement is propelled to or at a predetermined
depth, predetermined velocity, predetermined rate of
administration, predetermined angle, predetermined spatial
location, predetermined depth, predetermined time sequence, or
predetermined spatial pattern for delivery of the at least one
composition to a desired location of the at least one biological
tissue. In one embodiment, the velocity, rate, or angle of
administration of the one or more frozen particle compositions, or
frozen piercing implements are variable. In one embodiment, a
method of administering one or more frozen particle compositions,
or frozen piercing implements includes varying the rate, velocity,
or angle. In one embodiment, a method includes multiple
administrations of the one or more frozen particle compositions, or
frozen piercing implements, wherein at least two of the
administrations include different velocities, rates, or angles of
delivery.
In one embodiment, the at least one frozen particle composition; or
frozen piercing implement is propelled to or at a velocity of
approximately 1 m/s, approximately 5 m/s, approximately 10 m/s,
approximately 20 m/s, approximately 30 m/s, approximately 40 m/s,
approximately 50 m/s, approximately 60 m/s, approximately 70 m/s,
approximately 80 m/s, approximately 90 m/s, approximately 100 m/s,
approximately 200 m/s, approximately 300 m/s, approximately 400
m/s, approximately 500 m/s, approximately 600 m/s, approximately
700 m/s, approximately 800 m/s, approximately 900 m/s,
approximately 1000 m/s, approximately 1500 m/s, approximately 2000
m/s, approximately 3000 m/s, approximately 4000 m/s, approximately
5000 m/s, or any value greater or therebetween.
In one embodiment, the at least one frozen particle composition, or
frozen piercing implement is accelerated or ejected toward the at
least one substrate (such as a biological tissue) to a velocity of
approximately 1 m/s, approximately 5 m/s, approximately 10 m/s,
approximately 20 m/s, approximately 30 m/s, approximately 40 m/s,
approximately 50 m/s, approximately 60 m/s, approximately 70 m/s,
approximately 80 m/s, approximately 90 m/s, approximately 100 m/s,
approximately 200 m/s, approximately 300 m/s, approximately 400
m/s, approximately 500 m/s, approximately 600 m/s, approximately
700 m/s, approximately 800 m/s, approximately 900 m/s,
approximately 1000 m/s, approximately 1500 m/s, approximately 2000
m/s, approximately 3000 m/s, approximately 4000 m/s, approximately
5000 m/s, or any value greater or therebetween.
In one embodiment, delivering at least one frozen particle
composition, or frozen piercing implement to at least one substrate
(such as a biological tissue) includes accelerating, ejecting, or
propelling a plurality of frozen particle compositions, or frozen
piercing implements toward the at least one substrate (including a
biological tissue). In one embodiment, the plurality of frozen
particle compositions, or frozen piercing implements is
administered to at least one substrate including at a predetermined
angle, a predetermined velocity, a predetermined rate of
administration, a predetermined spatial pattern, a predetermined
spatial location, a predetermined time sequence, or a predetermined
depth. Such a plurality of particles may include one embodiment
wherein two or more frozen particle compositions, or frozen
piercing implements of the plurality include one or more similar
agents. Likewise, a plurality of frozen particle compositions, or
frozen piercing implements may include one embodiment wherein two
or more frozen particle compositions, or frozen piercing implements
include one or more dissimilar agents. In one embodiment, the rate,
velocity, or angle at which the one or more frozen particle
compositions, or frozen piercing implements are administered is
variable.
In one embodiment, a device for making and propelling one or more
frozen particle compositions, or frozen piercing implements
includes at least one particle accelerator. In one embodiment, the
particle accelerator includes a linear, circular or spherical
accelerator. In one embodiment, the particle accelerator includes a
spiral, conical, helical, or conic-helical accelerator. In one
embodiment, the particle accelerator includes a 2-dimensional or
3-dimensional accelerator.
For example, in a 2-dimensional spiral, polar coordinates can be
expressed as a function of angle .theta., where the radius r is a
continuous monotonic function of angle .theta., and a and b are
arbitrary positive real constants. For example, several embodiments
are shown in FIG. 135 A-K.
As described herein, a plurality of frozen particle compositions,
or frozen piercing implements may include one or more subsets,
which can be delivered or administered in an order of operations.
In one embodiment, the order of operations includes delivery or
administration in a pattern. In one embodiment, the order of
operations includes delivery or administration in a predetermined
pattern. In one embodiment, the order of operations includes
delivery or administration in sequential order. In one embodiment,
the order of operations includes delivery or administration at
random.
For embodiments described herein, those having skill in the art
will recognize that the state of the art has progressed to the
point where there is little distinction left between hardware,
software, and/or firmware implementations of aspects of systems;
the use of hardware, software, and/or firmware is generally (but
not always, in that in certain contexts the choice between hardware
and software can become significant) a design choice representing
cost vs. efficiency tradeoffs. Those having skill in the art will
appreciate that there are various vehicles by which processes
and/or systems and/or other technologies described herein can be
effected (e.g., hardware, software, and/or firmware), and that the
preferred vehicle will vary with the context in which the processes
and/or systems and/or other technologies are deployed. For example,
if an implementer determines that speed and accuracy are paramount,
the implementer may opt for a mainly hardware and/or firmware
vehicle; alternatively, if flexibility is paramount, the
implementer may opt for a mainly software implementation; or, yet
again alternatively, the implementer may opt for some combination
of hardware, software, and/or firmware. Hence, there are several
possible vehicles by which the processes and/or devices and/or
other technologies described herein can be effected, none of which
is inherently superior to the other in that any vehicle to be
utilized is a choice dependent upon the context in which the
vehicle will be deployed and the specific concerns (e.g., speed,
flexibility, or predictability) of the implementer, any of which
may vary. Those skilled in the art will recognize that optical
aspects of implementations will typically employ optically-oriented
hardware, software, and or firmware.
In some implementations described herein, logic and similar
implementations may include software or other control structures.
Electronic circuitry, for example, may have one or more paths of
electrical current constructed and arranged to implement various
functions as described herein. In some implementations, one or more
media can be configured to bear a device-detection implementation
when such media hold or transmit device detection instructions
operable to perform as described herein. In some variants, for
example, implementations may include an update or modification of
existing software or firmware, or of gate arrays or programmable
hardware, such as by performing a reception of or a transmission of
one or more instructions in relation to one or more operations
described herein. Alternatively or additionally, in some variants,
an implementation may include special-purpose hardware, software,
firmware components, and/or general-purpose components executing or
otherwise invoking special-purpose components. Specifications or
other implementations can be transmitted by one or more instances
of tangible transmission media as described herein, optionally by
packet transmission or otherwise by passing through distributed
media at various times.
Alternatively or additionally, implementations may include
executing a special-purpose instruction sequence or invoking
circuitry for enabling, triggering, coordinating, requesting, or
otherwise causing one or more occurrences of virtually any
functional operations described herein. In some variants,
operational or other logical descriptions herein can be expressed
as source code and compiled or otherwise invoked as an executable
instruction sequence. In some contexts, for example, C++ or other
code sequences can be compiled or implemented in high-level
descriptor languages (e.g., a logic-synthesizable language, a
hardware description language, a hardware design simulation, and/or
other such similar mode(s) of expression). For example, some or all
of the logical expression can be manifested as a Verilog-type
hardware description or other circuitry model before physical
implementation in hardware. Those skilled in the art will recognize
how to obtain, configure, and optimize suitable transmission or
computational elements, material supplies, actuators, or other
structures in light of these teachings.
As indicated in FIGS. 7-9, one embodiment, a method 700 includes
comparing 710 information regarding at least one aspect of
administering at least one frozen particle composition (or frozen
piercing implement) to at least one subject and information
regarding at least one clinical outcome following receipt by the at
least one subject of at least one frozen particle composition (or
frozen piercing implement); and providing output information
optionally based on the comparison.
In one embodiment, the method includes determining at least one
statistical correlation 720. In one embodiment, the method includes
counting the occurrence of at least one clinical outcome 730. In
one embodiment, the method includes determining at least one
correlation before the administration of the at least one frozen
particle composition (or frozen piercing implement) 735. In one
embodiment, information regarding at least one aspect of
administering at least one frozen particle composition (or frozen
piercing implement) includes information regarding the amount of at
least one frozen particle composition (or frozen piercing
implement) or therapeutic agent administered to at least one
biological tissue of a subject 740. In one embodiment, the
information regarding at least one aspect of administering or
delivering at least one frozen particle composition (or frozen
piercing implement) includes information regarding at least one
dimension of biological tissue penetration 750. In one embodiment,
information regarding the at least one dimension of biological
tissue penetration includes information regarding at least one of
depth, width, or breadth of administration of at least one frozen
particle composition (or frozen piercing implement) to at least one
biological tissue of at least one subject 760.
In one embodiment, the information regarding at least one aspect of
administering at least one frozen particle composition (or frozen
piercing implement) includes information regarding two or more
subjects with one or more common attributes 770. In one embodiment,
the one or more common attributes include genetic attributes,
mental attributes, or psychological attributes 780. In at least on
embodiment, the one or more common attributes include genotype
attributes or phenotype attributes 790.
In one embodiment, the one or more common attributes 797 include at
least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; genetic profile; proteomic profile; lipidomic
profile, glycomic profile, system biology profile, partial or whole
genetic sequence; partial or whole proteomic sequence; medical
history; lymph condition, circulatory condition, respiratory
condition, or blood condition.
In one embodiment, the output information 810 includes at least one
of a response signal, a comparison code, a comparison plot, a
diagnostic code, a treatment code, a test code, a code indicative
of at least one treatment received, a code indicative of at least
one prescribed treatment step, a code indicative of at least one
vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of an
administered or delivered frozen particle composition (or frozen
piercing implement). In one embodiment, the at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one cellular or tissue source 820. In one
embodiment, the information regarding at least one tissue source
includes information regarding at least one abnormal cellular or
tissue source 830. In one embodiment, the information regarding at
least one cellular or tissue source includes information regarding
at least one type of cell or tissue 840. In one embodiment, the
cellular or tissue source includes at least one cell or biological
tissue described herein.
In one embodiment, the at least one frozen particle composition,
frozen piercing implement, frozen piercing implement device, or
therapeutic composition includes at least one of nitrogen, carbon
dioxide, hydrogen oxide, helium, neon, xenon, krypton, chlorine,
bromine, methane, oxygen, air, argon, polyethylene glycol, acetone,
ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 850.
In one embodiment, the at least one frozen particle composition,
frozen piercing implement, frozen piercing implement device, or
therapeutic composition includes at least one major dimension of
approximately one decimeter or less, or approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer
or less, or any value therebetween 860.
In one embodiment, the at least one frozen particle composition,
frozen piercing implement, frozen piercing implement device, or
therapeutic composition includes one or more reinforcement agents
870. In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes one or more explosive materials 880. In one
embodiment, the receipt by the at least one subject of at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition is pursuant to at least one clinical trial
900.
In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 910. In one embodiment, the method further comprises
suggesting the inclusion of one or more of the at least one subject
in at least one clinical trial 920. In one embodiment, the method
further comprises suggesting the exclusion of one or more of the at
least one subject in at least one clinical trial 930. In certain
instances, multiple subjects from multiple clinical trials are
included. In one embodiment, the method further includes using one
or more of the at least one comparison to predict at least one
clinical outcome regarding at least one second subject 940. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 950. In one embodiment, the
at least one second subject is a plurality of people; and the
method further comprises segregating subject identifiers associated
with the plurality of people in reference to the predicted at least
one clinical outcome 960. In one embodiment, the at least one
second subject is a plurality of people; and the method further
comprises determining the eligibility of the at least one second
subject for the at least one clinical trial 970.
As indicated in FIGS. 10-12, at least one aspect includes a method
1000 relating to predicting a clinical outcome of administering at
least one frozen particle therapeutic composition (or frozen
piercing implement) to at least one biological tissue of at least
one first subject includes determining a similarity or a
dissimilarity in information regarding at least one aspect of
administering at least one therapeutic composition (or frozen
piercing implement) to the at least one biological tissue of the at
least one first subject to information regarding at least one
aspect of administering at least one therapeutic composition (or
frozen piercing implement) to the at least one biological tissue of
the at least one second subject, wherein the at least one second
subject attained a clinical outcome following receipt of the at
least one frozen particle therapeutic composition(or frozen
piercing implement); and providing output information optionally
based on the determination 1010.
In one embodiment, the information regarding the at least one
aspect of administering at least one frozen particle therapeutic
composition (or frozen piercing implement) includes information
1020 regarding the amount of at least one frozen particle
therapeutic composition (or frozen piercing implement) or
therapeutic agent delivered to at least one biological tissue of a
subject. In one embodiment, the information regarding the at least
one aspect of administering at least one frozen particle
therapeutic composition (or frozen piercing implement) includes
information 1030 regarding at least one dimension of biological
tissue penetration. In one embodiment, the information regarding
the at least one dimension of biological tissue penetration
includes information 1040 regarding at least one of depth, width,
or breadth of delivery of at least one frozen particle therapeutic
composition (or frozen piercing implement) to at least one
biological tissue of at least one subject; or information 1050
regarding two or more subjects with common attributes.
In one embodiment, the one or more common attributes include
genetic attributes, mental attributes, or psychological attributes
1060. In at least on embodiment, the one or more common attributes
include genotype attributes or phenotype attributes 1070.
In one embodiment, the one or more common attributes 1080 include
at least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; genetic profile; proteomic profile; partial or
whole genetic sequence; medical history; partial or whole proteomic
sequence; lymph condition, or blood condition.
In one embodiment, the output information 1100 includes at least
one of a response signal, a comparison code, a comparison plot, a
diagnostic code, a treatment code, a test code, a code indicative
of at least one treatment received, a code indicative of at least
one prescribed treatment step, a code indicative of at least one
vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of an
administered or delivered frozen particle composition (or frozen
piercing implement) or therapeutic composition. In one embodiment,
the at least one aspect of cellular or tissue abrasion or ablation
includes information regarding at least one cellular or tissue
source 1110. In one embodiment, the information regarding at least
one tissue source includes information regarding at least one
abnormal cellular or tissue source 1120. In one embodiment, the
information regarding at least one cellular or tissue source
includes information regarding at least one type of cell or tissue
1130. In one embodiment, the cellular or tissue source includes at
least one cell or biological tissue described herein.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) includes at least one of nitrogen,
carbon dioxide, hydrogen oxide, helium, neon, xenon, krypton,
chlorine, bromine, methane, oxygen, air, argon, polyethylene
glycol, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon
tetrachloride, hexane, methylene chloride, carboxylic acid, saline,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether
1140.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes at
least one major dimension of approximately one decimeter or less,
or approximately one centimeter or less, approximately one
millimeter or less, approximately one micrometer or less,
approximately one nanometer or less, or any value therebetween
1150.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes one
or more reinforcement agents 1160. In one embodiment, the at least
one frozen particle composition (or frozen piercing implement) or
therapeutic composition includes one or more explosive materials
1170.
In one embodiment, the receipt by the at least one subject of at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 1200. In one embodiment, the method further
comprises determining at least one correlation before the
administration or delivery of the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition to at least one subject 1210. The at least one subject
includes, but is not limited to at least one subject described
herein.
In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition or therapeutic composition 1220. In one embodiment, the
method further comprises suggesting the inclusion of one or more of
the at least one subject in at least one clinical trial 1230. In
one embodiment, the method further comprises suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial 1240. In certain instances, multiple subjects
from multiple clinical trials are included. In one embodiment, the
method further includes using one or more of the at least one
comparison to predict at least one clinical outcome regarding at
least one second subject 1250. In one embodiment, the at least one
second subject has not received the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 1260. In one embodiment, the method includes predicting
at least one clinical outcome involving the at least one second
subject, and the at least one second subject is a plurality of
people; and the method further comprises segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome 1270.
In one embodiment, the at least one second subject is a plurality
of people; and the method further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 1280.
As shown in FIGS. 13-15, one embodiment includes a system 1300
including at least one computer program 1310, configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to one or more instructions
1320 for comparing information regarding at least one aspect of at
least one therapeutic administration of at least one frozen
particle composition (or frozen piercing implement) or therapeutic
composition to at least one subject. In one embodiment, information
1330 regarding amount of the at least one frozen particle
composition, (or frozen piercing implement), therapeutic
composition, or therapeutic agent administered to at least one
biological tissue of at least one subject. In one embodiment,
information regarding at least one aspect of at least one
therapeutic administration of at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes information regarding at least one dimension
of biological tissue penetration 1340. In one embodiment,
information regarding at least one aspect of at least one
therapeutic administration of at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes information regarding at least one of depth,
width, or breadth of administration of at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition to at least one biological tissue of at least one
subject 1350. In one embodiment, information regarding at least one
aspect of at least one therapeutic administration includes
information regarding two or more subjects with one or more common
attributes 1360. In one embodiment, the computing device is
configured to communicate with at least one imaging device. In one
embodiment, the computing device is configured to communicate with
at least one printing device. In one embodiment, the computing
device is configured to communicate with at least one input device
1370.
In one embodiment, the information regarding at least one aspect of
therapeutic administration of at least one therapeutic composition
includes information regarding at least one cellular or tissue
source 1400; information regarding at least one abnormal cellular
or tissue source 1410; or information regarding at least one type
of cell or tissue 1420. In one embodiment, at least one frozen
particle composition (or frozen piercing implement) or therapeutic
composition includes at least one of nitrogen, carbon dioxide,
hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine,
methane, oxygen, air or argon. In one embodiment, the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition includes at least one of polyethylene
glycol, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon
tetrachloride, hexane, methylene chloride, carboxylic acid, saline,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether 1430. In
one embodiment, at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition includes at least
one major dimension of approximately one decimeter or less,
approximately one centimeter or less, approximately one millimeter
or less, approximately one micrometer or less, approximately one
nanometer or less, or any value therebetween 1440. In one
embodiment, the at least one frozen particle composition (or frozen
piercing implement) or therapeutic composition includes one or more
reinforcement agents 1450 or one or more explosive materials
1460.
In one embodiment, the receipt by the at least one subject of at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 1500. In one embodiment, the system further
comprises determining at least one correlation before the delivery
or administration of the at least one frozen particle composition
(or frozen piercing implement) or therapeutic composition to at
least one subject 1510.
In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 1520. In one embodiment, the instructions further
comprise suggesting the inclusion of one or more of the at least
one subject in at least one clinical trial 1530. In certain
instances, multiple subjects from multiple clinical trials are
included.
In one embodiment, the instructions include suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial 1540.
In one embodiment, a method includes using one or more of the at
least one comparison to predict at least one clinical outcome
regarding at least one second subject 1550. In one embodiment, the
at least one second subject has not received the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition 1560. In one embodiment, the at least one
second subject is a plurality of people; and further comprising
segregating subject identifiers associated with the plurality of
people in reference to the predicted at least one clinical outcome
1570.
In one embodiment, the using one or more of the at least one
comparison, wherein the at least one second subject is a plurality
of people; and further comprising determining the eligibility of
the at least one second subject for the at least one clinical trial
1580.
As indicated in FIG. 16, one embodiment relates to a system 1600
including at least one computer program 1610 configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to one or more instructions
1620 for comparing information regarding at least one aspect of at
least one therapeutic administration of at least one frozen
particle therapeutic composition (or frozen piercing implement) to
at last one subject, and information regarding at least one frozen
particle therapeutic composition (or frozen piercing implement)
involving at least one biological tissue of at least one subject;
and one or more instructions for applying one or more comparisons
to the information regarding the at least one aspect of therapeutic
administration of at least one frozen particle therapeutic
composition (or frozen piercing implement) to a plurality of
people. In one embodiment, the computer program includes one or
more instructions 1630 for segregating subject identifiers
associated with the plurality of people in reference to at least
one of the one or more applied comparisons. In one embodiment,
information regarding at least one aspect of at least one
therapeutic administration includes information 1640 regarding the
amount of at least one frozen particle composition (or frozen
piercing implement), therapeutic composition or therapeutic agent
administered to at least one biological tissue of at least one
subject; information 1650 regarding at least one dimension of
biological tissue penetration; information 1660 regarding at least
one of depth, width, or breadth of administration of at least one
frozen particle therapeutic composition to at least one biological
tissue of at least one subject. In one embodiment, the computer
program includes one or more instructions 1670 for segregating
individual identifiers associated with the plurality of people in
reference to at least one characteristic shared by two or more
subjects in the plurality of people.
As shown in FIG. 17, one embodiment relates to a computer program
product 1700 that includes a signal bearing medium 1710 bearing at
least one of one or more instructions 1720 for receiving a first
input associated with a first possible dataset, the first possible
dataset including data representative of one or more measurements
relating to one or more physical attributes of a first subject; one
or more instructions 1730 for comparing a value associated with the
first possible dataset with a second dataset including values
representative of predictive regimen parameters from a second
subject with one or more similar or dissimilar physical attributes;
one or more instructions 1740 for determining from the comparison
at least one frozen particle therapeutic composition (or frozen
piercing implement) regimen for the first subject and output
information; one or more instructions 1750 for accessing the first
possible dataset in response to the first input; one or more
instructions 1760 for generating the first possible dataset in
response to the first input; one or more instructions 1770 for
determining a graphical illustration of the first possible dataset;
one or more instructions 1780 for determining a graphical
illustration of the second possible dataset; and at least one
generated output optionally based on the determination.
In one embodiment, the computer program product includes a signal
bearing medium that includes a computer-readable medium 1790. In
one embodiment, the signal bearing medium of the computer program
product includes a recordable medium 1792.
In one embodiment, the computer program product includes a signal
bearing medium that includes a communications medium 1794.
As indicated in FIG. 18, one embodiment relates to a computer
program product 1800 that includes a signal bearing medium 1810
bearing at least one of one or more instructions 1820 for
processing a first possible dataset, the first possible dataset
including data representative of one or more measurements relating
to one or more physical attributes of a first subject; one or more
instructions 1830 for comparing a value associated with the first
possible dataset with a second dataset including values
representative of predictive regimen parameters from a second
subject with one or more similar or dissimilar physical attributes;
one or more instructions 1840 for determining from the comparison
at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition treatment regimen for the
first subject, and output information.
As indicated in FIG. 19, one embodiment relates to a computer
program product 1900 that includes a signal bearing medium 1910
bearing at least one of one or more instructions 1920 responsive to
a first possible dataset, the first possible dataset including data
representative of one or more measurements relating to one or more
physical attributes of a first subject; one or more instructions
1930 for comparing a value associated with the first possible
dataset with a second dataset including values representative of
predictive regimen parameters for a second subject with one or more
similar or dissimilar physical attributes; one or more instructions
1940 for determining from the comparison at least one frozen
particle composition (or frozen piercing implement) or therapeutic
composition treatment regimen for the first subject; and output
information optionally based on the determination.
As shown in FIG. 20, one embodiment relates to a computer program
product 2000 that includes a signal bearing medium 2010 bearing at
least one of one or more instructions 2020 for receiving a first
input associated with a first possible dataset, the first possible
dataset including data representative of one or more measurements
relating to one or more physical attributes of a subject; one or
more instructions 2030 for comparing a value associated with the
first possible dataset with a second dataset including values
representative of parameters relating to one or more expected
biological changes following administration of one or more frozen
particle compositions (or frozen piercing implements) or
therapeutic compositions; one or more instructions 2040 for
determining from the comparison at least one biological change
following administration of one or more frozen particle
compositions (or frozen piercing implements) or therapeutic
compositions to the subject; at least one generated output
optionally based on the determination.
In one embodiment, the computer program product includes one or
more instructions 2050 for accessing the first possible dataset in
response to the first input. In one embodiment, the computer
program product includes one or more instructions 2060 for
generating the first possible dataset in response to the first
input.
In one embodiment, the computer program product includes one or
more instructions 2070 for determining a graphical illustration of
the first possible dataset. In one embodiment, the computer program
product includes one or more instructions 2080 for determining a
graphical illustration of the second possible dataset. In one
embodiment, the signal bearing medium includes a computer-readable
medium 2090. In one embodiment, the signal bearing medium includes
a recordable medium 2092. In one embodiment, the signal bearing
medium includes a communications medium 2094.
As indicated in FIG. 21, one embodiment a computer program product
2100 includes a signal bearing medium 2110 bearing at least one of
one or more instructions 2120 for processing a first input
associated with a first possible dataset, the first possible
dataset including data representative of one or more measurements
relating to one or more physical attributes of a subject; one or
more instructions 2130 for comparing a value associated with the
first possible dataset with a second dataset including values
representative of parameters relating to one or more expected
biological changes following administration of one or more frozen
particle compositions (or frozen piercing implements) or
therapeutic compositions; one or more instructions 2140 for
determining from the comparison at least one biological change
following administration of one or more frozen particle
compositions (or frozen piercing implements) or therapeutic
compositions to the subject; at least one generated output
optionally based on the determination.
As shown in FIG. 22, one embodiment relates to a computer program
product 2200 includes a signal bearing medium 2210 bearing at least
one of one or more instructions 2220 responsive to a first possible
dataset, the first possible dataset including data representative
of one or more measurements relating to one or more physical
attributes of a subject; one or more instructions 2230 for
comparing a value associated with the first possible dataset with a
second dataset including values representative of parameters
relating to one or more expected biological changes following
administration of one or more frozen particle compositions (or
frozen piercing implements) or therapeutic compositions; one or
more instructions 2240 for determining from the comparison at least
one biological change following administration of one or more
frozen particle compositions (or frozen piercing implements) or
therapeutic compositions to the subject; and output information
optionally based on the determination.
As indicated in FIGS. 23-25, one embodiment, a method 2300 includes
comparing 2310 information regarding at least one aspect of
cellular or tissue abrasion or ablation of at least one biological
tissue of at least one subject and information regarding at least
one clinical outcome following receipt by the at least one subject
of at least one frozen particle composition (or frozen piercing
implement) or therapeutic composition; and providing output
information optionally based on the determination. In one
embodiment, the method includes determining at least one
statistical correlation 2320. In one embodiment, the method
includes counting the occurrence of at least one clinical outcome
2330. In one embodiment, the information regarding at least one
aspect of cellular or tissue abrasion or ablation includes
information regarding quantity of cells or tissue removed or
destroyed 2340. In one embodiment, the information regarding at
least one aspect of cellular or tissue abrasion or ablation
includes information regarding at least one dimension of cellular
or tissue removal or destruction, or removal or destruction of
other materials, such as plaque, extracellular matrix, collagen,
elastin, protein, or other materials 2350. In one embodiment,
information regarding the at least one dimension of cellular
removal or destruction includes information regarding at least one
of depth, width, or breadth of cellular removal or destruction
2360.
In one embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding two or more subjects with one or more common attributes
2370. In one embodiment, the one or more common attributes include
genetic attributes, mental attributes, or psychological attributes
2380. In at least on embodiment, the one or more common attributes
include genotype attributes or phenotype attributes 2390.
In one embodiment, the one or more common attributes 2397 include
at least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; genetic profile; proteomic profile; partial or
whole genetic sequence; medical history; partial or whole proteomic
sequence; lymph condition, or blood condition.
In one embodiment, the output information 2410 includes at least
one of a response signal, a comparison code, a comparison plot, a
diagnostic code, a treatment code, a test code, a code indicative
of at least one treatment received, a code indicative of at least
one prescribed treatment step, a code indicative of at least one
vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of a
delivered or administered frozen particle composition (or frozen
piercing implement). In one embodiment, the at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one cellular or tissue source 2420. In one
embodiment, the information regarding at least one tissue source
includes information regarding at least one abnormal cellular or
tissue source 2430. In one embodiment, the information regarding at
least one cellular or tissue source includes information regarding
at least one type of cell or tissue 2440. In one embodiment, the
cellular or tissue source includes at least one cell or biological
tissue described herein.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes at
least one of nitrogen, carbon dioxide, hydrogen oxide, helium,
neon, xenon, krypton, chlorine, bromine, methane, oxygen, air,
argon, polyethylene glycol, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 2450.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) includes at least one major dimension of
approximately one decimeter or less, or approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer
or less, or any value therebetween 2460.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) includes one or more reinforcement
agents 2470. In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) includes one or more
explosive materials 2480. In one embodiment, the receipt by the at
least one subject of at least one frozen particle composition (or
frozen piercing implement) is pursuant to at least one clinical
trial 2500. In one embodiment, the method further comprises
determining at least one correlation 2510 before the delivery or
administration of the at least one frozen particle composition (or
frozen piercing implement) to at least one subject. The at least
one subject includes, but is not limited to at least one subject
described herein.
In one embodiment, the method includes creating at least one
inclusion criterion and at least one exclusion criterion for a
clinical trial involving the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition 2515. In one embodiment, the method further comprises
suggesting the inclusion of one or more of the at least one subject
in at least one clinical trial 2520. In one embodiment, the method
further comprises suggesting the exclusion of one or more of the at
least one subject in at least one clinical trial 2530. In certain
instances, multiple subjects from multiple clinical trials are
included. In one embodiment, the method further includes using one
or more of the at least one correlation to predict at least one
clinical outcome regarding at least one second subject 2540. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 2550. In one embodiment, the
method further comprises predicting at least one clinical outcome
involving the at least one second subject, wherein the at least one
second subject is a plurality of people; and segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome 2560. In one
embodiment, the at least one second subject is a plurality of
people; and the method further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 2570.
As indicated in FIGS. 26-28, one embodiment relates to a method
2600 of predicting a clinical outcome of at least one frozen
particle composition (or frozen piercing implement) treatment for
at least one first subject includes determining 2610 a similarity
or a dissimilarity in information regarding at least one aspect of
cellular or tissue abrasion or ablation of at least one biological
tissue of at least one first subject to information regarding at
least one aspect of cellular or tissue abrasion or ablation of at
least one biological tissue of at least one second subject, wherein
the at least one second subject attained a clinical outcome
following receipt of the at least one frozen particle composition
or therapeutic composition; and providing output information
optionally based on the determination.
In one embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding the quantity of cells or tissue removed or destroyed
2620. In one embodiment, the information regarding at least one
aspect of cellular or tissue abrasion or ablation includes
information regarding at least one dimension of cellular, tissue,
or other material removal or destruction 2630. In one embodiment,
the at least one dimension of cellular removal or destruction
includes information regarding at least one of depth, width, or
breadth of cellular removal or destruction 2640. In one embodiment,
the information regarding at least one aspect of cellular or tissue
abrasion or ablation includes information regarding two or more
subjects with one or more common attributes 2650.
In one embodiment, the one or more common attributes include but
are not limited to genetic attributes, mental attributes, or
psychological attributes 2660. In one embodiment, the one or more
common attributes include genotype attributes or phenotype
attributes 2670.
In one embodiment, the one or more common attributes include at
least one of height; weight; medical diagnosis; familial
background; results on one or more medical tests; ethnic
background; body mass index; age; presence or absence of at least
one disease or condition; species; ethnicity; race; allergies;
gender; thickness of epidermis; thickness of dermis; thickness of
stratum corneum; keratin deposition; collagen deposition; blood
vessel condition; skin condition; hair or fur condition; muscle
condition; tissue condition; organ condition; nerve condition;
brain condition; presence or absence of at least one biological,
chemical, or therapeutic agent in the subject; pregnancy status;
lactation status; medical history; genetic profile; proteomic
profile; partial or whole genetic sequence; partial or whole
proteomic sequence; lymph condition, medical history, or blood
condition 2680.
In one embodiment, the output information includes at least one of
a response signal, a comparison code, a comparison plot, a
diagnostic code, a treatment code, a test code, a code indicative
of at least one treatment received, a code indicative of at least
one prescribed treatment step, a code indicative of at least one
vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of a
delivered or administered frozen particle composition (or frozen
piercing implement) 2700.
In one embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one cellular or tissue source 2710. In one
embodiment, the cellular or tissue source includes but is not
limited to at least one biological tissue or cell described herein.
In one embodiment, the information regarding at least one tissue
source includes information regarding at least one abnormal
cellular or tissue source 2720. In one embodiment, the information
regarding at least one cellular or tissue source includes
information regarding at least one type of cell or tissue 2730. In
one embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information
regarding at least one type of cell or tissue.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes at
least one of nitrogen, carbon dioxide, hydrogen oxide, helium,
neon, xenon, krypton, chlorine, bromine, methane, oxygen, air or
argon. In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) or therapeutic
composition includes at least one of polyethylene glycol, acetone,
ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 2740.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes at
least one major dimension of approximately one decimeter or less,
or approximately one centimeter or less, or approximately one
millimeter or less, or approximately one micrometer or less, or
approximately one nanometer or less, or any value therebetween
2750.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes one
or more reinforcement agents 2760. In one embodiment, the at least
one frozen particle composition (or frozen piercing implement) or
therapeutic composition includes one or more explosive materials
2770.
In one embodiment, the receipt by the at least one subject of at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 2800. In one embodiment, the method includes
creating at least one inclusion criterion and at least one
exclusion criterion for a clinical trial involving the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition 2810. In one embodiment, the method further
comprises suggesting the inclusion of one or more of the at least
one subject in at least one clinical trial 2820. In certain
instances, multiple subjects from multiple clinical trials are
included. In one embodiment, the method includes suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial 2830.
In one embodiment, a method includes using one or more of the at
least one determination to predict at least one clinical outcome
regarding at least one second subject 2840. In one embodiment, the
at least one second subject has not received the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition 2850. In one embodiment, the at least one
second subject is a plurality of people; and the method further
comprises segregating subject identifiers associated with the
plurality of people in reference to the predicted at least one
clinical outcome 2860.
In one embodiment, the using one or more of the at least one
comparison, wherein the at least one second subject is a plurality
of people; and the method further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 2870.
As indicated in FIGS. 29-30, at least one aspect relates to a
system 2900 that includes at least one computing device 2910; one
or more instructions 2920 that when executed on the at least one
computing device cause the at least one computing device to receive
a first input associated with a first possible dataset, the first
possible dataset including data representative of one or more
measurements relating to one or more physical attributes of a first
subject; one or more instructions 2930 that when executed on the at
least one computing device cause the at least one computing device
to compare a value associated with the first possible dataset with
a second dataset including values representative of predictive
regimen parameters related to a second subject with one or more
similar or dissimilar physical attributes; one or more instructions
2940 that when executed on the at least one computing device cause
the at least one computing device to determine from the comparison
at least one frozen particle composition (or frozen piercing
implement) treatment regimen for the first subject; and at least
one generated output optionally based on the determination; one or
more instructions 2950 that when executed on the at least one
computing device cause the at least one computing device to access
the first possible dataset in response to the first input; one or
more instructions 2960 that when executed on the at least one
computing device cause the at least one computing device to
generate the first possible dataset in response to the first input;
one or more instructions 2970 that when executed on the at least
one computing device cause the at least one computing device to
determine a graphical illustration of the possible dataset; or one
or more instructions 3000 that when executed on the at least one
computing device cause the at least one computing device to
determine a graphical illustration of the second possible dataset.
In one embodiment, the treatment regimen includes at least one of
cellular or tissue removal, cellular or tissue ablation,
debridement, delivery of at least one therapeutic agent, cleaning
one or more wounds, oxygenating wounds, removing material from at
least one biological tissue, or removing material from at least one
blood vessel 3005. In at least one nitrogen, carbon dioxide,
hydrogen oxide, helium, neon, xenon, krypton, chlorine, bromine,
methane, oxygen, air, argon, polyethylene glycol, acetone, ethyl
acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 3008.
In one embodiment, the at least one computing device includes one
or more desktop computer, workstation computer, computing system
including a cluster of processors, a networked computer, a tablet
personal computer, a laptop computer, a mobile device, a mobile
telephone, or a personal digital assistant computer 3010. In one
embodiment, the at least one computing device is configured to
communicate with a database to access the first possible dataset
3020. In one embodiment, the at least one computing device is
configured to communicate with a frozen particle composition (or
frozen piercing implement) selecting apparatus, a frozen particle
composition (or frozen piercing implement) generating apparatus, or
both 3030.
As shown in FIGS. 31-32, at least one aspect relates to a system
3100 including circuitry 3110 for receiving a first input
associated with a first possible dataset, the first possible
dataset including data representative of one or more measurements
relating to one or more physical attributes of a first subject;
circuitry 3120 for comparing a value associated with the first
possible dataset with a second dataset including values
representative of predictive regimen parameters related to a second
subject with one or more similar or dissimilar physical attributes;
circuitry 3125 for determining from the comparison at least one
frozen particle composition (or frozen piercing implement)
treatment regimen for the first subject; circuitry 3128 for
selecting at least one of quality or quantity related to one or
more frozen particle compositions (or frozen piercing implements),
method of administration of one or more frozen particle
compositions (or frozen piercing implements), administration
location of one or more frozen particle compositions (or frozen
piercing implements), content of one or more frozen particle
compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), decrease in physical dimension of one
or more frozen particle compositions (or frozen piercing
implements) or time interval between at least two deliveries with
one or more frozen particle compositions (or frozen piercing
implements).
In one embodiment, the system includes circuitry 3130 for
determining from the comparison at least one frozen particle
composition (or frozen piercing implement) treatment regimen for
the first subject; and circuitry 3140 for providing output
information optionally based on the comparison. In one embodiment,
the circuitry for receiving a first input associated with a first
possible dataset includes circuitry 3200 for receiving one or more
measurements relating to one or more physical attributes including
at least one of height; weight; body mass index; age; presence or
absence of at least one disease or condition; species; ethnicity;
race; allergies; gender; thickness of epidermis; thickness of
dermis; thickness of stratum corneum; keratin deposition; collagen
deposition; blood vessel condition; skin condition; hair or fur
condition; muscle condition; tissue condition; organ condition;
nerve condition; brain condition; presence or absence of at least
one biological, chemical, or therapeutic agent in the subject;
pregnancy status; lactation status; genetic profile; medical
history; proteomic profile; partial or whole genetic sequence;
partial or whole proteomic sequence; medical history; lymph
condition, or blood condition.
In one embodiment, the system includes circuitry 3210 for selecting
the combination of at least two parameters selected from quality or
quantity related to one or more frozen particle compositions (or
frozen piercing implements), method of administration of one or
more frozen particle compositions (or frozen piercing implements),
administration location of one or more frozen particle compositions
(or frozen piercing implements), content of one or more frozen
particle compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), decrease in a physical dimension of
one or more frozen particle compositions (or frozen piercing
implements), or time interval between at least two administrations
or deliveries with one or more frozen particle compositions (or
frozen piercing implements).
In one embodiment, the system includes circuitry 3220 for selecting
the combination of at least two parameters selected from quality or
quantity related to one or more frozen particle compositions (or
frozen piercing implements), method of administration of one or
more frozen particle compositions (or frozen piercing implements),
administration location of one or more frozen particle compositions
(or frozen piercing implements), content of one or more frozen
particle compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), decrease in a physical dimension of
one or more frozen particle compositions (or frozen piercing
implements), or time interval between at least two administrations
with one or more frozen particle compositions (or frozen piercing
implements).
In one embodiment, the system includes circuitry 3230 for selecting
at least one of a clinical outcome; secondary effects related to
the treatment; disease stage; longevity; or vaccination
administration. In one embodiment, the clinical outcome 3240
includes a positive clinical outcome or a negative clinical
outcome. In one embodiment, the clinical outcome includes one or
more adverse effect, failure to attain a clinical endpoint of a
clinical trial, failing to attain a beneficial effect, or
measurement of at least one biochemical, biological or
physiological parameter 3250.
FIGS. 33-35 illustrate a partial view of a system 3300 including at
least one computer program 3310 configured with a computer-readable
medium, for use with at least one computer system and wherein the
computer program includes a plurality of instructions including but
not limited to one or more instructions 3320 for determining at
least one comparison between information regarding at least one
aspect of cellular or tissue abrasion or ablation of at least one
biological tissue of at least one subject and information regarding
at least one clinical outcome following receipt by the at least one
subject of at least one frozen particle composition (or frozen
piercing implement). In one embodiment, the system includes one or
more instructions 3330 for determining at least one statistical
correlation. In one embodiment, the system includes one or more
instructions 3340 for counting the occurrence of at least one
clinical outcome. In one embodiment, information regarding at least
one aspect of cellular or tissue abrasion or ablation includes
information 3350 regarding quantity of cells or tissue removed or
destroyed; information 3360 regarding at least one dimension of
cellular, tissue or other material removal or destruction;
information 3370 regarding at least one of depth, width, or breadth
of cellular removal or destruction; or information 3380 regarding
two or more subjects with one or more common attributes. In one
embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information 3400
regarding at least one cellular or tissue source, including
information 3410 regarding at least one abnormal cellular or tissue
source or information 3420 regarding at least one type of cell or
tissue.
In one embodiment, the at least one frozen particle composition (or
frozen piercing implement) or therapeutic composition includes at
least one of polyethylene glycol, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, acetic acid, benzene, carbon tetrachloride, hexane,
methylene chloride, carboxylic acid, saline, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether 3430. In one embodiment, at least one
frozen particle composition (or frozen piercing implement) includes
at least one major dimension of approximately one decimeter or
less, approximately one centimeter or less, approximately one
millimeter or less, approximately one micrometer or less,
approximately one nanometer or less, or any value therebetween
3440. In one embodiment, the at least one frozen particle
composition (or frozen piercing implement) includes one or more
reinforcement agents 3450. In one embodiment, the at least one
frozen particle composition (or frozen piercing implement) includes
one or more explosive materials 3460.
In one embodiment, the receipt by the at least one subject of at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition is pursuant to at least one
clinical trial 3500. In one embodiment, the system further
comprises one or more instructions for determining at least one
comparison before the delivery or administration of the at least
one frozen particle composition (or frozen piercing implement) or
therapeutic composition to at least one subject 3510.
In one embodiment, the system includes one or more instructions for
creating at least one inclusion criterion and at least one
exclusion criterion for a clinical trial involving the at least one
frozen particle composition (or frozen piercing implement) or
therapeutic composition 3520. In one embodiment, the system further
comprises one or more instructions for suggesting the inclusion of
one or more of the at least one subject in at least one clinical
trial 3530. In certain instances, multiple subjects from multiple
clinical trials are included.
In one embodiment, the system further includes one or more
instructions for suggesting the exclusion of one or more of the at
least one subject in at least one clinical trial 3540. In one
embodiment, the system includes one or more instructions for using
one or more of the at least one comparison to predict at least one
clinical outcome regarding at least one second subject 3550. In one
embodiment, the at least one second subject has not received the at
least one frozen particle composition (or frozen piercing
implement) or therapeutic composition 3560. In one embodiment, the
system includes predicting at least one clinical outcome involving
the at least one second subject, wherein the at least one second
subject is a plurality of people; and segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome 3570. In one
embodiment, the at least one second subject is a plurality of
people; and the system further comprises determining the
eligibility of the at least one second subject for the at least one
clinical trial 3580.
As indicated in FIG. 36, at least one aspect relates to a system
3600 that includes at least one computer program 3610, configured
with a computer-readable medium, for use with at least one computer
system and wherein the computer program includes a plurality of
instructions including but not limited to one or more instructions
3620 for comparing information regarding at least one aspect of
cellular or tissue abrasion or ablation of at least one biological
tissue of at least one subject and information regarding at least
one frozen particle composition (or frozen piercing implement)
involving the at least one biological tissue of at least one
subject; and one or more instructions 3630 for applying one or more
comparisons to information regarding at least one aspect of
cellular or tissue abrasion or ablation regarding a plurality of
people.
In one embodiment, one or more instructions 3640 for segregating
subject identifiers associated with the plurality of people in
reference to at least one of the one or more applied comparisons.
In one embodiment, the information regarding at least one aspect of
cellular or tissue abrasion or ablation includes information 3650
regarding quantity of cells or tissue removed or destroyed;
information 3660 regarding at least one dimension of cellular,
tissue or other material removal or destruction; or information
3670 regarding at least one of depth, width, or breadth of cellular
removal or destruction. In one embodiment, the system includes one
or more instructions 3680 for segregating individual identifiers
associated with the plurality of people in reference to at least
one characteristic shared by two or more subjects of the plurality
of people.
As indicated in FIG. 37, at least one aspect relates to a method
3700 comprising accepting a first input 3710 associated with at
least one characteristic of at least one biological tissue to be at
least partially constructed or at least partially reconstructed;
accepting a second input 3720 associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) including at least one agent. In one embodiment, the at
least one agent 3730 includes one or more of a therapeutic agent,
adhesive agent, abrasive, reinforcement agent, explosive material,
or biological remodeling agent. In one embodiment, administering
3740 the one or more frozen particle compositions (or frozen
piercing implements) includes administering the one or more frozen
particle compositions (or frozen piercing implements) to at least
one substrate. In one embodiment, the at least one substrate 3750
includes one or more of a cell, tissue, organ, structure, or
device.
In one embodiment, the method includes processing results 3760 of
the first input and the second input. In one embodiment, processing
results of the first input and the second input includes
electronically processing 3770 results of the first input and the
second input. In one embodiment, processing results of the first
input and the second input includes 3780 electronically processing
results of the first input and the second input by utilizing one or
more of Gaussian smoothing, scaling, homomorphic filtering,
parametric estimation techniques, Boolean operations, Monte Carlo
simulations, wavelet based techniques, mirroring, smoothing,
gradient weighted partial differential equation smoothing, NURBS,
polygonal modeling, splines and patches modeling, algorithmic
execution, logical decision-making, result prediction, Finite
Element Analysis, or modification of a CAD design.
As indicated in FIG. 38, in one embodiment, the first input 3810
includes one or more values related to the at least one
characteristic of at least one biological tissue. In one
embodiment, the first input includes one or more spatial addresses
3820 associated with the at least one characteristic of at least
one biological tissue. In one embodiment, the first input includes
one or more of x, y, or z coordinates 3830 associated with the at
least one characteristic of at least one biological tissue.
In one embodiment, the at least one characteristic 3840 of at least
one biological tissue to be at least partially constructed or at
least partially reconstructed includes one or more of:
morphological feature, anatomical feature, histological feature,
tissue hierarchical level, scaffold feature, vascular structure
feature, heterogenous tissue feature, mechanical feature,
volumetric feature, geometric feature, volumetric representation,
mechanical feature, deformation, kinematic feature, surface contour
feature, cytometric feature, cell aggregation, cell growth,
cell-cell interaction, cell-tissue interaction, biomimetic design,
cell pattern, cell deposition, organ hierarchical level, tissue
microstructure, cellular microstructure, cell junction feature,
tissue junction feature, cell-tissue classification, hard tissue
classification, soft tissue classification, tumor diagnosis, or
other feature.
In one embodiment, the at least one characteristic 3850 of at least
one biological tissue includes one or more of cellular type,
cellular function, cellular size, cellular constitution, cellular
architecture, cellular durability, cellular source, tissue type,
tissue constitution, tissue size, tissue shape, tissue function,
tissue architecture, tissue source, tissue durability, organ type,
organ constitution, organ size, organ shape, organ function, organ
architecture, organ source, or organ durability. In one embodiment,
the first input 3860 includes one or more temporal addresses
associated with the at least one characteristic of at least one
biological tissue.
As indicated in FIG. 39, in one embodiment, the first input 3910
includes one or more values derived from at least one image of the
at least one biological tissue. In one embodiment, the at least one
image 3920 includes one or more images acquired by one or more of
laser, holography, x-ray crystallography, optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, electrical-impedance monitoring, microscopy,
spectrometry, flow cytommetry, radioisotope imaging, thermal
imaging, multiphoton calcium-imaging, photography, or in silico
generation.
In one embodiment, the at least one biological tissue 3930 is
located in at least one of in situ, in vitro, in vivo, in utero, in
planta, in silico, or ex vivo. In one embodiment, the at least one
biological tissue 3940 is at least partially located in at least
one subject. In one embodiment, the method further comprises
accepting a third input 3950 associated with at least one feature
of the at least one subject. In one embodiment, the at least one
feature 3960 of the at least one subject includes one or more of
age, gender, genotype, phenotype, proteomic profile, or health
condition.
As indicated in FIGS. 40-41, in one embodiment, the processing
results 4010 of the first input and the second input includes
determining at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue with one or more frozen particle compositions (or
frozen piercing implements) from one or more values derived from at
least one image of the at least one biological tissue. In one
embodiment, the second input 4020 includes one or more values
related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions (or frozen piercing implements) to the at least one
substrate. In one embodiment, 4130 the one or more values related
to the at least one parameter of constructing or reconstructing the
at least one biological tissue includes one or more predictive
values.
In one embodiment, the at least one parameter 4030 of at least
partially constructing or at least partially reconstructing the at
least one biological tissue includes one or more of porosity of the
at least one substrate, pore size of the at least one substrate,
interconnectivity of the pores of the at least one substrate,
transport properties of the at least one substrate, cell-tissue
formation of the at least one substrate, mechanical strength of the
at least one substrate, ability for attachment or distribution of
the at least one agent included in the one or more frozen particle
compositions (or frozen piercing implements) to the at least one
substrate, ability for attachment or distribution of one or more
cells or tissues to the at least one substrate, facilitation of at
least one nutrient, or tissue formation or tissue growth associated
with the at least one substrate.
In one embodiment, the at least one parameter 4040 of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) includes one
or more of: design of plot or model for administration of one or
more frozen particle compositions(or frozen piercing implements),
constitution of the one or more frozen particle compositions (or
frozen piercing implements), formulation of the one or more frozen
particle compositions (or frozen piercing implements), size of the
one or more frozen particle compositions (or frozen piercing
implements), shape of the one or more frozen particle compositions
(or frozen piercing implements), angle of administration of the one
or more frozen particle compositions (or frozen piercing
implements), velocity of administration of the one or more frozen
particle compositions (or frozen piercing implements), quantity of
frozen particle compositions (or frozen piercing implements)
administered, rate of administration of more than one frozen
particle composition (or frozen piercing implement), spatial
location for administration of one or more frozen particle
compositions (or frozen piercing implements), temporal location for
administration of one or more frozen particle compositions (or
frozen piercing implements), method of administration of one or
more frozen particle compositions (or frozen piercing implements),
timing of administration of one or more frozen particle
compositions (or frozen piercing implements), modulation of
administration of one or more frozen particle compositions (or
frozen piercing implements), deposition of one or more frozen
particle compositions (or frozen piercing implements), or rate of
deposition of at least one agent.
In one embodiment, the at least one parameter 4110 of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) includes at
least one parameter relating to at least partially ablating or at
least partially abrading one or more surfaces of the at least one
biological tissue with the one or more frozen particle compositions
(or frozen piercing implements).
In one embodiment, the at least one parameter 4120 of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) includes at
least one parameter relating to administering at least one of a
therapeutic agent, adhesive agent, biological remodeling agent,
reinforcement agent, abrasive, or explosive material with the one
or more frozen particle compositions (or frozen piercing
implements).
In one embodiment, the spatial location 4140 for administration of
one or more frozen particle compositions (or frozen piercing
implements)includes one or more of x, y, or z coordinates. In one
embodiment, the processing results 4150 includes comparing at least
one value related to the first input associated with the at least
one characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed with at
least one value related to at least one image of a target
biological tissue. In one embodiment 4160, the image of a target
biological tissue includes an image of a similar biological tissue,
or an image of a dissimilar biological tissue.
As indicated in FIG. 42, the processing results 4210 includes
comparing at least one value related to the second input associated
with the at least one parameter of at least partially constructing
or at least partially reconstructing the at least one biological
tissue with at least one value related to another administration of
one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 4220, the processing results
includes determining one or more differences in at least one value
related to the first input and at least one value related to at
least one image of the at least one biological tissue or a similar
biological tissue. In one embodiment 4230, the processing results
includes determining one or more differences in at least one value
related to the second input associated with the at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue and at least one
value related to another administration of one or more frozen
particle compositions (or frozen piercing implements) to the at
least one substrate.
In one embodiment 4240, the processing results includes generating
one or more protocols for administering the one or more frozen
particle compositions (or frozen piercing implements). In one
embodiment 4250, the processing results includes generating one or
more blueprints for administering the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
4260, the one or more blueprints include at least one of a
two-dimensional plot or a three-dimensional model. In one
embodiment 4270, the one or more blueprints include at least one
representation of at least one of organ anatomy, morphology, tissue
heterogeneity, scale of vascular system, geometry, internal
architecture of an organ or tissue, internal or external boundary
distinction of a tissue or organ, topology, or tomography.
As indicated in FIG. 43, the processing results 4310 includes:
comparing one or more values related to the one or more
characteristics of the at least one biological tissue that are
determined at two or more different times to obtain one or more
characteristic comparisons; comparing one or more values related to
the at least one parameter of at least partially constructing or at
least partially reconstructing the at least one biological tissue
at two or more different times to obtain one or more parameter
comparisons; comparing the one or more characteristic comparisons
with the one or more parameter comparisons to obtain one or more
characteristic-characteristic/parameter-parameter comparisons; and
comparing the one or more
characteristic-characteristic/parameter-parameter comparisons to
one or more substantially similar results obtained for one or more
other at least partially constructed or at least partially
reconstructed biological tissues. In one embodiment 4320, the
administering one or more frozen particle compositions (or frozen
piercing implements) includes depositing the at least one agent on
the at least one substrate.
As indicated in FIG. 44, the method further comprises 4410
displaying results of the processing. In one embodiment 4420, the
displaying results of the processing includes displaying the
results on one or more active displays. In one embodiment 4430, the
displaying results of the processing includes displaying the
results on one or more passive displays. In one embodiment 4440,
the displaying results of the processing includes displaying the
results of the processing in at least one of numeric format,
graphical format, or audio format.
In one embodiment 4450, the displaying results of the processing
includes displaying a comparison of at least one biological tissue
that has been at least partially constructed or at least partially
reconstructed. In one embodiment 4460, the displaying results of
the processing includes displaying a comparison of at least one
subject with one or more other subjects. In one embodiment 4470,
the displaying results of the processing includes displaying one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
image of a biological tissue. In one embodiment 4480, the
displaying results of the processing includes displaying one or
more differences in the comparison of at least one value related to
the second input and at least one value related to another
administration of one or more frozen particle compositions (or
frozen piercing implements).
As indicated in FIG. 45, the method further comprises transmitting
4510 one or more signals that include information related to the
processing results of the first input and the second input. In one
embodiment 4520, the transmitting one or more signals includes
transmitting one or more signals associated with selection of one
or more frozen particle compositions (or frozen piercing
implements) for administration. In one embodiment 4530, the
transmitting one or more signals includes transmitting one or more
signals associated with selection of one or more of a biological
remodeling agent, adhesive agent, abrasive, therapeutic agent,
reinforcement agent, or explosive material associated with the one
or more frozen particle compositions (or frozen piercing
implements). In one embodiment 4540, the transmitting one or more
signals includes transmitting one or more signals associated with
comparing the information related to the processing results of the
first input and the second input.
As indicated in FIG. 46, the one or more frozen particle
compositions (or frozen piercing implements) 4610 include one or
more frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, methane, or diethyl
ether.
In one embodiment 4620, the at least one agent includes one or more
of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 4630, at least one of the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
As indicated in FIG. 47, the one or more explosive materials 4710
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 4720, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
In at least one embodiment 4730, the one or more reinforcement
agents include one or more of polyaramid, vinylester matrix, metal,
ceramic, cotton, hemp, fiberglass, cellulose, broad carbide,
aromatic polyamide, nylon, silk, rayon, acetate, modacrylic,
olefin, acrylic, polyester, aromatic polyester, poly-lactic acid,
vinyon, saran, spandex, vinalon, aromatic nylon, vinylidene
chloride, modal, polybenzimidazole, sulfur, lyocell, orlon, zylon,
high-performance polyethylene, polypyridobenzimidazole, vectran,
acrylonitrile rubber, glass, copper, iron, steel, sodium,
potassium, calcium, zinc, manganese, carbon, magnesium, silicon,
silica, frozen hydrogen oxide ice, plant matter, animal matter, or
mineral matter.
As indicated in FIG. 48, the therapeutic agent 4810 includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
In one embodiment 4820 the at least one biological remodeling agent
includes one or more of a blood cell, chondrocyte, endothelial
cell, hepatocyte, keratinocyte, myocyte, osteoblast, osteoclast,
osteocyte, mesenchymal cell, stem cell, progenitor cell, or
fibroblast. In one embodiment, 4830, the at least one biological
remodeling agent includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 4840, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 4850, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIGS. 49-51, a method 4900 comprises accepting
input 4910 associated with at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements);
administering 4920 one or more frozen particle compositions (or
frozen piercing implements) including at least one agent;
wherein 4930 the at least one agent includes one or more of a
biological remodeling agent, therapeutic agent, reinforcement
agent, explosive material, abrasive, or adhesive agent; evaluating
4940 the at least one biological tissue for one or more indicators
related to deposition of at least one agent, tissue formation, or
tissue growth; and transmitting 5110 one or more signals that
include information related to the accepting input and information
related to the evaluating the at least one biological tissue.
In one embodiment 4950, the evaluating at least one biological
tissue for one or more indicators includes evaluating at least one
of an assay, image, or gross assessment of the at least one
biological tissue prior to, during, or subsequent to at least one
administration of the one or more frozen particle compositions (or
frozen piercing implements). In one embodiment 4960, the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay.
In one embodiment 5020, the image includes at least one image
acquired by one or more of laser, holography, x-ray
crystallography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation. In one
embodiment 5030, wherein the one or more indicators of tissue
formation or growth include at least one of cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
carbohydrate production, carbohydrate secretion, fat production,
fat secretion, or protein secretion.
In one embodiment 5040, the input associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) includes one or more of constitution of the one or more
frozen particle compositions (or frozen piercing implements),
formulation of the one or more frozen particle compositions (or
frozen piercing implements), size of the one or more frozen
particle compositions (or frozen piercing implements), shape of the
one or more frozen particle compositions (or frozen piercing
implements), angle of administration of the one or more frozen
particle compositions (or frozen piercing implements), velocity of
administration of the one or more frozen particle compositions (or
frozen piercing implements), quantity of frozen particle
compositions (or frozen piercing implements) administered, rate of
administration of more than one frozen particle composition (or
frozen piercing implement), spatial location for administration of
one or more frozen particle compositions (or frozen piercing
implements), temporal location for administration of one or more
frozen particle compositions (or frozen piercing implements),
method of administration of one or more frozen particle
compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), modulation of administration of one or
more frozen particle compositions (or frozen piercing implements),
deposition of one or more frozen particle compositions (or frozen
piercing implements), or rate of deposition of at least one
agent.
In one embodiment 5120, the transmitting one or more signals
includes transmitting one or more signals associated with selection
of one or more frozen particle compositions (or frozen piercing
implements) for administration. In one embodiment 5130, the
transmitting one or more signals includes transmitting one or more
signals associated with selection of one or more of a biological
remodeling agent, adhesive agent, abrasive, therapeutic agent,
reinforcement agent, or explosive material associated with the one
or more frozen particle compositions (or frozen piercing
implements). In one embodiment 5140, the administering one or more
frozen particle compositions (or frozen piercing implements)
includes administering the one or more frozen particle compositions
(or frozen piercing implements) to at least one substrate. In one
embodiment 5150, the at least one substrate includes one or more of
a cell, tissue, organ, structure, or device. In one embodiment
5160, the one or more frozen particle compositions (or frozen
piercing implements) include one or more frozen particles including
at least one of hydrogen oxide, nitrogen, oxygen, air, helium,
neon, argon, xenon, chlorine, bromine, carbon dioxide, acetone,
ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
tetrahydrofuran, acetronitrile, acetic acid, n-butanol,
isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, methane,
or diethyl ether.
As indicated in FIG. 52, the at least one agent 5210 includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 5220, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent is substantially in the form of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
In one embodiment 5230, the one or more explosive materials include
at least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal.
In one embodiment 5240, the at least one adhesive agent includes
one or more of an acrylic polymer or copolymer, acrylamide polymer
or copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
As indicated in FIG. 53, the one or more reinforcement agents 5310
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 5320, the therapeutic agent includes at least one
of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 5330, the at least
one biological remodeling agent includes one or more of a blood
cell, chondrocyte, endothelial cell, hepatocyte, keratinocyte,
myocyte, osteoblast, osteoclast, osteocyte, mesenchymal cell, stem
cell, progenitor cell, or fibroblast.
In one embodiment 5340, the at least one biological remodeling
agent includes one or more of calcium phosphate, albumin, cytokine,
pegylated cytokine, bone, cartilage, globulin, fibrin, thrombin,
glutaraldehyde-crosslinked pericardium, hide powder, hyaluronic
acid, hydroxylapatite, keratin, ligament, nitinol, nucleic acid
polymers, polyethylene, polylethylene glycol, polyethylene glycol
diacrylate, polyethylene terephthalate fiber, polyglycol,
polylactate, polytetrafluoroethylene, polylactic acid, polyglycolic
acid, polycaprolactone, PURAMATRIX.TM. self-assembly peptide
hydrogel fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, silicone, polyurethane,
ceramic powder, elastin, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or
gelatin.
In one embodiment 5350, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, Type X collagen, elastin
fibers, or soluble elastin.
As indicated in FIG. 54, a method 5400 comprises receiving 5410 one
or more signals that include information related to accepting input
associated with at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions (or frozen piercing implements); receiving 5420 one or
more signals that include information related to evaluating the at
least one biological tissue for one or more indicators of tissue
formation or growth; and processing 5430 the information related to
the input associated with at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue and the information related to the
evaluating the at least one biological tissue. In one embodiment
5440, the evaluating at least one biological tissue for one or more
indicators includes evaluating at least one of an assay, image, or
gross assessment of the at least one biological tissue prior to,
during, or subsequent to at least one administration of one or more
frozen particle compositions (or frozen piercing implements).
In one embodiment 5450, the assay includes at least one technique
that includes spectroscopy, microscopy, electrochemical detection,
polynucleotide detection, histological examination, biopsy
analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 5460, the image includes at
least one image acquired by one or more of optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, x-ray crystallography, laser, holography,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation.
As indicated in FIG. 55, the one or more indicators 5510 of tissue
formation or growth include at least one of: cell migration, cell
attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
carbohydrate production, carbohydrate secretion, fat production,
fat secretion, or protein secretion.
In one embodiment 5520, the input associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue includes one or
more of constitution of the one or more frozen particle
compositions (or frozen piercing implements), formulation of the
one or more frozen particle compositions (or frozen piercing
implements), size of the one or more frozen particle compositions
(or frozen piercing implements), shape of the one or more frozen
particle compositions (or frozen piercing implements), angle of
administration of the one or more frozen particle compositions (or
frozen piercing implements), velocity of administration of the one
or more frozen particle compositions (or frozen piercing
implements), quantity of frozen particle compositions (or frozen
piercing implements) administered, rate of administration of more
than one frozen particle composition(or frozen piercing implement),
spatial location for administration of one or more frozen particle
compositions (or frozen piercing implements), temporal location for
administration of one or more frozen particle compositions (or
frozen piercing implements), method of administration of one or
more frozen particle compositions (or frozen piercing implements),
timing of administration of one or more frozen particle
compositions (or frozen piercing implements), modulation of
administration of one or more frozen particle compositions (or
frozen piercing implements), deposition of one or more frozen
particle compositions (or frozen piercing implements), or rate of
deposition of at least one agent.
In one embodiment 5530, the receiving one or more signals includes
receiving one or more signals associated with selection of one or
more frozen particle compositions
(or frozen piercing implements) for administration. In one
embodiment 5540, the receiving one or more signals includes
receiving one or more signals associated with the selection of at
least one of a biological remodeling agent, adhesive agent,
abrasive, therapeutic agent, reinforcement agent, or explosive
material associated with the one or more frozen particle
compositions (or frozen piercing implements).
As indicated in FIG. 56, in one embodiment 5610, the administering
one or more frozen particle compositions (or frozen piercing
implements) includes administering the one or more frozen particle
compositions (or frozen piercing implements) to at least one
substrate. In one embodiment 5620, the at least one substrate
includes one or more of a cell, tissue, organ, structure, or
device. In one embodiment 5630, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, methane, or diethyl
ether.
In one embodiment 5640, the at least one agent includes one or more
of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 5650, the adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent is substantially in the form of at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, oligosaccharide, polysaccharide, glycopeptide, glycolipid,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, cell
nucleus, acid, base, buffer, protic solvent, aprotic solvent,
nitric oxide, nitric oxide synthase, nitrous oxide, amino acid,
micelle, polymer, bone cement, copolymer, cell receptor, adhesion
molecule, cytokine, chemokine, immunoglobulin, antibody, antigen,
platelet, extracellular matrix, blood, plasma, cell ligand,
zwitterionic material, cationic material, oligonucleotide,
nanotube, or piloxymer.
As indicated in FIG. 57, the one or more explosive materials 5710
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 5720, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or gelatin.
In one embodiment 5730, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 5740, the therapeutic agent includes at least one
of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
In one embodiment 5810, the at least one biological remodeling
agent includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast. In one embodiment 5820, the at least one
biological remodeling agent includes one or more of calcium
phosphate, albumin, cytokine, pegylated cytokine, bone, cartilage,
globulin, fibrin, thrombin, glutaraldehyde-crosslinked pericardium,
hide powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 5830, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin.
In one embodiment 5840, the at least one biological remodeling
agent is included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIG. 59, a method 5900 comprises comparing
information 5910 regarding at least one parameter for at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject by administering one or
more frozen particle compositions (or frozen piercing implements)
to the at least one subject and information regarding at least one
clinical outcome following receipt by the at least one subject of
one or more frozen particle compositions (or frozen piercing
implements); and providing output information 5920. In one
embodiment 5930, the output information is based on the comparison.
In one embodiment 5940, the method further comprises determining at
least one statistical correlation. In one embodiment 5950, the
method further comprises counting the occurrence of at least one
clinical outcome. In one embodiment 5960, the information regarding
at least one parameter of at least partially constructing or at
least partially reconstructing at least one biological tissue of a
subject includes information regarding quantity of cells or tissue
at least partially constructed or at least partially reconstructed.
In one embodiment 5970, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of a subject includes
information regarding at least one cellular or tissue source. In
one embodiment 5980, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of a subject includes
information regarding at least one abnormal cellular or tissue
source. In one embodiment 5990, the information regarding at least
one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of a
subject includes information regarding at least one type of cell or
tissue.
As indicated in FIG. 60, the at least one agent 6010 includes at
least one agent including at least one adhesive agent, abrasive,
reinforcement agent, therapeutic agent, biological remodeling
agent, or explosive material. In one embodiment 6020, the
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of a subject includes information regarding at
least one dimension of at least one agent deposited. In one
embodiment 6030, the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
subject includes information regarding at least one dimension of at
least one depth, width, or breadth of cellular, tissue, or other
material removal or destruction. In one embodiment 6040, the
information regarding at least one clinical outcome following
receipt by the at least one subject of one or more frozen particle
compositions (or frozen piercing implements) includes information
regarding two or more subjects with one or more common
attributes.
In one embodiment 6050, the one or more common attributes include
one or more of genetic attributes, mental attributes, proteomic
attributes, phenotypic attributes, or psychological attributes. In
one embodiment 6060, the one or more common attributes include one
or more of height, weight, medical diagnosis, familial background,
results on one or more medical tests, ethnic background, body mass
index, age, presence or absence of at least one disease or
condition, species, ethnicity, race, allergies, gender, thickness
of tissue, blood vessel condition, hair or fur condition, skin
condition, tissue condition, muscle condition, organ condition,
nerve condition, brain condition, presence or absence of at least
one biological, chemical, or therapeutic agent in the subject,
pregnancy status, lactation status, genetic profile, proteomic
profile, partial or whole genetic sequence, partial or whole
proteomic sequence, medical condition, medical history, or blood
condition.
As indicated in FIG. 61, the output information 6110 includes at
least one of a response signal, comparison code, comparison plot,
diagnostic code, treatment code, test code, code indicative of at
least one treatment received, code indicative of at least one
prescribed treatment step, code indicative of at least one
vaccination administered, code indicative of at least one
therapeutic agent administered, code indicative of at least one
diagnostic agent administered, code indicative of at least one
interaction of an administered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispertion or location of at least one administered agent; code
indicative of at least one detection material administered; code
indicative of the depth of penetration of an administered agent,
code indicative of the depth of deposition of an administered
agent, or a code indicative of the condition of at least one
location of an administered frozen particle composition (or frozen
piercing implement).
In one embodiment 6120, receipt by the at least one subject of one
or more frozen particle compositions (or frozen piercing
implements) is pursuant to at least one clinical trial. In one
embodiment 6130, the method further comprises determining at least
one correlation before the administration of the one or more frozen
particle compositions (or frozen piercing implements) to the at
least one subject.
In one embodiment 6140, the method further comprises creating at
least one inclusion criterion and at least one exclusion criterion
for a clinical trial involving the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
6150, the method further comprises suggesting the inclusion of one
or more of the at least one subject in at least one clinical trial.
In one embodiment 6160, the method further comprises suggesting the
exclusion of one or more of the at least one subject in at least
one clinical trial.
As indicated in FIG. 62, the method further comprising using one or
more of the at least one correlation 6210 to predict at least one
clinical outcome regarding at least one second subject. In one
embodiment 6220, the at least one second subject has not received
the one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 6230, the method further comprises
predicting at least one clinical outcome involving the at least one
second subject, wherein the at least one second subject is a
plurality of people; and segregating subject identifiers associated
with the plurality of people in reference to the predicted at least
one clinical outcome. In one embodiment 6240, the method further
comprises determining the eligibility of the at least one second
subject for the at least one clinical trial.
In one embodiment 6250, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, methane, or diethyl
ether.
As indicated in FIG. 63, the at least one agent 6310 includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 6320, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent is substantially in the form of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer. In one
embodiment 6330, the one or more explosive materials include at
least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal. In one
embodiment 6340, the at least one adhesive agent includes one or
more of an acrylic polymer or copolymer, acrylamide polymer or
copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
As indicated in FIG. 64, the one or more reinforcement agents 6410
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 6420, the therapeutic agent includes at least one
of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 6430, the at least
one biological remodeling agent includes one or more of a blood
cell, chondrocyte, endothelial cell, hepatocyte, keratinocyte,
myocyte, osteoblast, osteoclast, osteocyte, mesenchymal cell, stem
cell, progenitor cell, or fibroblast.
As indicated in FIG. 65, the at least one biological remodeling
agent 6510 includes one or more of calcium phosphate, albumin,
cytokine, pegylated cytokine, bone, cartilage, globulin, fibrin,
thrombin, glutaraldehyde-crosslinked pericardium, hide powder,
hyaluronic acid, hydroxylapatite, keratin, ligament, nitinol,
nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 6520, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 6530, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIG. 66, a method 6600 of predicting a clinical
outcome of one or more frozen particle composition (or frozen
piercing implement) treatments for at least one first subject,
comprises determining 6610 a similarity or a dissimilarity in
information regarding at least one parameter for at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one first subject by administering
one or more frozen particle compositions (or frozen piercing
implements) to the at least one first subject with information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one second subject, wherein the at least one second
subject 6620 attained a clinical outcome following receipt of one
or more frozen particle compositions (or frozen piercing
implements); and providing output information 6630.
In one embodiment 6640, providing output information is based on
the determination. In one embodiment 6650, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least second subject includes information regarding quantity
of cells or tissue at least partially constructed or at least
partially reconstructed. In one embodiment 6660, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one first subject includes information regarding at
least one cellular or tissue source. In one embodiment 6670, the
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one first subject includes
information regarding at least one abnormal cellular or tissue
source.
As indicated in FIG. 67, the information 6710 regarding at least
one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one first subject includes information regarding at least one type
of cell or tissue. In one embodiment 6720, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one second subject includes information regarding at
least one type of cell or tissue. In one embodiment 6730, the at
least one agent includes one or more of an adhesive agent,
abrasive, reinforcement agent, therapeutic agent, biological
remodeling agent, or explosive material. In one embodiment 6740,
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one first subject includes
information regarding at least one dimension of at least one agent
deposited.
In one embodiment 6750, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
second subject includes information regarding at least one
dimension of at least one agent deposited. In one embodiment 6760,
the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one second subject includes
information regarding at least one dimension of at least one depth,
width, or breadth of cellular, tissue, or other material removal or
destruction. In one embodiment 6770, the information regarding at
least one parameter of at least partially constructing or at least
partially reconstructing at least one biological tissue of at least
one first subject includes information regarding at least one
dimension of at least one depth, width, or breadth of cellular,
tissue, or other material removal or destruction.
As indicated in FIG. 68, the information 6810 regarding at least
one clinical outcome following receipt by the at least one second
subject of one or more frozen particle compositions (or frozen
piercing implements) includes information regarding two or more
subjects with one or more common attributes. In one embodiment
6820, the one or more common attributes include one or more of
genetic attributes, mental attributes, proteomic attributes,
phenotypic attributes, or psychological attributes. In one
embodiment 6830, the one or more common attributes include one or
more of height, weight, medical diagnosis, familial background,
results on one or more medical tests, ethnic background, body mass
index, age, presence or absence of at least one disease or
condition, species, ethnicity, race, allergies, gender, thickness
of tissue, blood vessel condition, hair or fur condition, skin
condition, tissue condition, muscle condition, organ condition,
nerve condition, brain condition, presence or absence of at least
one biological, chemical, or therapeutic agent in the subject,
pregnancy status, lactation status, genetic profile, proteomic
profile, partial or whole genetic sequence, partial or whole
proteomic sequence, medical condition, medical history, or blood
condition. In one embodiment 6840, the output information includes
at least one of a response signal, comparison code, comparison
plot, diagnostic code, treatment code, test code, code indicative
of at least one treatment received, code indicative of at least one
prescribed treatment step, code indicative of at least one
vaccination administered, code indicative of at least one
therapeutic agent administered, code indicative of at least one
diagnostic agent administered, code indicative of at least one
interaction of an administered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one administered agent; code
indicative of at least one detection material administered; code
indicative of the depth of penetration of an administered agent,
code indicative of the depth of deposition of an administered
agent, or a code indicative of the condition of at least one
location of an administered frozen particle composition (or frozen
piercing implement).
As indicated in FIG. 69, in one embodiment 6910, receipt by the at
least one second subject of one or more frozen particle
compositions (or frozen piercing implements) is pursuant to at
least one clinical trial. In one embodiment 6920, the method
further comprises determining at least one correlation before the
administration of the one or more frozen particle compositions (or
frozen piercing implements) to the at least one first subject. In
one embodiment 6930, the method further comprises creating at least
one inclusion criterion and at least one exclusion criterion for a
clinical trial involving the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
6940, the method further comprises suggesting the inclusion of one
or more of the at least one first subject in at least one clinical
trial. In one embodiment 6950, the method further comprises
suggesting the exclusion of one or more of the at least one first
subject in at least one clinical trial.
In one embodiment 6960, the method further comprises using one or
more of the at least one correlation to predict at least one
clinical outcome regarding at least one second subject. In one
embodiment 6970, the at least one second subject has not received
the one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 6980, the method further comprises
predicting at least one clinical outcome involving the at least one
second subject, wherein the at least one second subject is a
plurality of people; and segregating subject identifiers associated
with the plurality of people in reference to the predicted at least
one clinical outcome.
As indicated in FIG. 70, in one embodiment 7010, the one or more
frozen particle compositions (or frozen piercing implements)
include one or more frozen particles including at least one of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 7020, the one or more frozen particle
compositions (or frozen piercing implements) include one or more of
an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 7030, the adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent is substantially in the form of at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, oligosaccharide, polysaccharide, glycopeptide, glycolipid,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, cell
nucleus, acid, base, buffer, protic solvent, aprotic solvent,
nitric oxide, nitric oxide synthase, nitrous oxide, amino acid,
micelle, polymer, bone cement, copolymer, cell receptor, adhesion
molecule, cytokine, chemokine, immunoglobulin, antibody, antigen,
platelet, extracellular matrix, blood, plasma, cell ligand,
zwitterionic material, cationic material, oligonucleotide,
nanotube, or piloxymer.
In one embodiment 7040, the one or more explosive materials include
at least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal.
As indicated in FIG. 71, the at least one adhesive agent 7110
includes one or more of an acrylic polymer or copolymer, acrylamide
polymer or copolymer polymer or copolymer, acrylamide polymer or
copolymer, polyacrylic acid, epoxy, urethane, gum arabic,
polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
In one embodiment 7120, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 7130, the therapeutic agent includes at least one
of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
As indicated in FIG. 72, the at least one biological remodeling
agent 7210 includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast. In one embodiment 7220, the at least one
biological remodeling agent includes one or more of calcium
phosphate, albumin, cytokine, pegylated cytokine, bone, cartilage,
globulin, fibrin, thrombin, glutaraldehyde-crosslinked pericardium,
hide powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 7230, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 7240, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIG. 73, a system 7300 comprises at least one
computing device 7310; one or more instructions 7340 that when
executed on the at least one computing device cause the at least
one computing device to receive a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more parameters for administering one or
more frozen particle compositions (or frozen piercing implements).
In one embodiment 7350, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive parameter for
administering one or more frozen particle compositions (or frozen
piercing implements).
In one embodiment 7320, the at least one computing device includes
one or more of a desktop computer, workstation computer, or
computing system. In one embodiment 7330, the at least one
computing system includes one or more of a cluster of processors, a
networked computer, a tablet personal computer, a laptop computer,
a mobile device, a mobile telephone, or a personal digital
assistant computer.
As indicated in FIG. 74, the system further comprises one or more
instructions 7460 that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the second possible dataset.
In one embodiment 7410, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one parameter for administering one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 7420, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one response based on the determination. In one embodiment 7430,
the system further comprises one or more instructions that when
executed on the at least one computing device cause the at least
one computing device to access the first possible dataset in
response to the first input.
In one embodiment 7440, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate the
first possible dataset in response to the first input.
In one embodiment 7450, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the first possible dataset.
As indicated in FIG. 75, a system 7510 comprises at least one
computing device 7520; one or more instructions 7560 that when
executed on the at least one computing device cause the at least
one computing device to receive a first input associated with a
first possible dataset, the first possible dataset including data
representative of one or more characteristics of at least one
biological tissue or organ to be at least partially constructed or
at least partially reconstructed by administering one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 7570, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive characteristic of at
least one biological tissue or organ to be at least partially
constructed or at least partially reconstructed by administering
one or more frozen particle compositions (or frozen piercing
implements).
In one embodiment 7530, the at least one computing device includes
one or more of a desktop computer, workstation computer, or
computing system. In one embodiment 7540, the at least one
computing system includes one or more of a cluster of processors, a
networked computer, a tablet personal computer, a laptop computer,
a mobile device, a mobile telephone, or a personal digital
assistant computer. In one embodiment 7550, the at least one
computing device is configured to communicate with at least one
apparatus for selecting or generating one or more frozen particle
compositions (or frozen piercing implements).
As indicated in FIG. 76, the system further comprises one or more
instructions 7610, that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the second possible dataset. In one
embodiment 7620, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one characteristic of the at least one
biological tissue or organ to be at least partially constructed or
at least partially reconstructed by administering one or more
frozen particle compositions (or frozen piercing implements). In
one embodiment 7630, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one response based on the determination.
In one embodiment 7640, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to access the first
possible dataset in response to the first input. In one embodiment
7650, the system further comprises one or more instructions that
when executed on the at least one computing device cause the at
least one computing device to generate the first possible dataset
in response to the first input. In one embodiment 7660, the system
further comprises one or more instructions that when executed on
the at least one computing device cause the at least one computing
device to determine a graphical illustration of the first possible
dataset.
As indicated in FIG. 77, a system 7700 comprises a signal-bearing
medium 7710 bearing one or more instructions 7720 for accepting a
first input associated with at least one characteristic of at least
one biological tissue to be at least partially constructed or at
least partially reconstructed by administering one or more frozen
particle compositions (or frozen piercing implements); one or more
instructions 7730 for accepting a second input associated with at
least one characteristic of at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) that include
at least one agent; and one or more instructions 7740 for
processing results of the first input and the second input. In one
embodiment 7750, the system further comprising one or more
instructions for displaying results of the processing.
In one embodiment 7760, the system further comprises one or more
instructions for transmitting one or more signals that include
information related to the processing results of the first input
and the second input. In one embodiment 7770, the system further
comprises one or more instructions for administering one or more
frozen particle compositions (or frozen piercing implements) that
include at least one agent including: biological remodeling agent,
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
or explosive material. In one embodiment, the system 7780 further
comprises one or more instructions for evaluating the at least one
biological tissue for one or more indicators relating to one or
more of: deposition of at least one agent, tissue formation, or
tissue growth.
In one embodiment 7790, the signal-bearing medium includes a
computer-readable medium. In one embodiment 7795, the
signal-bearing medium includes a recordable medium. In one
embodiment 7797, the signal-bearing medium includes a
communications medium.
As indicated in FIG. 78, a computer program product 7800 comprises
a signal-bearing medium 7810 bearing one or more instructions 7820
for accepting a first input associated with at least one
characteristic of at least one biological tissue to be at least
partially constructed or at least partially reconstructed by
administering one or more frozen particle compositions (or frozen
piercing implements); one or more instructions 7830 for accepting a
second input associated with at least one characteristic of at
least one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue by
administering one or more frozen particle compositions (or frozen
piercing implements) that include at least one agent; and one or
more instructions 7840 for processing results of the first input
and the second input.
In one embodiment 7850, the computer program product further
comprises one or more instructions for displaying results of the
processing. In one embodiment 7860, the computer program product
further comprises one or more instructions for transmitting one or
more signals that include information related to the processing
results of the first input and the second input. In one embodiment
7870, the computer program product further comprises one or more
instructions for administering one or more frozen particle
compositions (or frozen piercing implements) that include at least
one agent including biological remodeling agent, therapeutic agent,
adhesive agent, abrasive, reinforcement agent, or explosive
material.
In one embodiment 7880, the computer program product further
comprises one or more instructions for evaluating the at least one
biological tissue for one or more indicators relating to one or
more of deposition of at least one agent, tissue formation, or
tissue growth.
In one embodiment 7890, the signal-bearing medium includes a
computer-readable medium. In one embodiment 7895, the
signal-bearing medium includes a recordable medium. In one
embodiment 7897, the signal-bearing medium includes a
communications medium.
As indicated in FIG. 79, a system 7900 comprises circuitry 7910 for
accepting a first input associated with at least one characteristic
of at least one biological tissue to be at least partially
constructed or at least partially reconstructed by administering
one or more frozen particle compositions (or frozen piercing
implements); circuitry 7920 for accepting a second input associated
with at least one characteristic of at least one parameter of at
least partially constructing or at least partially reconstructing
the at least one biological tissue by administering one or more
frozen particle compositions (or frozen piercing implements) that
include at least one agent; and circuitry 7930 for processing
results of the first input and the second input. In one embodiment
7940, the system further comprises circuitry for displaying results
of the processing. In one embodiment 7950, the system further
comprises circuitry for transmitting one or more signals that
include information related to the processing results of the first
input and the second input. In one embodiment 7960, the system
further comprises circuitry for administering one or more frozen
particle compositions (or frozen piercing implements) that include
at least one agent including at least one biological remodeling
agent, therapeutic agent, adhesive agent, abrasive, reinforcement
agent, or explosive material. In one embodiment 7970, the system
further comprises circuitry for evaluating the at least one
biological tissue for one or more indicators relating to one or
more of deposition of at least one agent, tissue formation, or
tissue growth.
As indicated in FIG. 80, a system 8000 comprises at least at least
one computer program 8010, configured with a computer-readable
medium, for use with at least one computer system and wherein the
computer program includes a plurality of instructions including but
not limited to: one or more instructions 8020 for accepting a first
input associated with at least one characteristic of at least one
biological tissue to be at least partially constructed or at least
partially reconstructed by administering one or more frozen
particle compositions (or frozen piercing implements); one or more
instructions 8030 for accepting a second input associated with at
least one characteristic of at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) that include
at least one agent; and one or more instructions 8040 for
processing results of the first input and the second input.
In one embodiment 8050, the system further comprises one or more
instructions for displaying results of the processing. In one
embodiment 8060, the system further comprises one or more
instructions for transmitting one or more signals that include
information related to the processing results of the first input
and the second input.
In one embodiment 8070, the system further comprises one or more
instructions for administering one or more frozen particle
compositions (or frozen piercing implements) that include at least
one agent including biological remodeling agent, therapeutic agent,
adhesive agent, abrasive, reinforcement agent, or explosive
material.
In one embodiment 8080, the system further comprises one or more
instructions for evaluating the at least one biological tissue for
one or more indicators relating to one or more of deposition of at
least one agent, tissue formation, or tissue growth.
As indicated in FIG. 81, the system further comprises at least one
computing device 8110. In one embodiment 8120, the at least one
computing device is configured to communicate with at least one
printing device, at least one imaging device, or at least one input
device.
As indicated in FIG. 82, a system 8200 comprises means 8210 for
accepting a first input associated with at least one characteristic
of at least one biological tissue to be at least partially
constructed or at least partially reconstructed; means 8220 for
accepting a second input associated with at least one parameter of
at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) including at least one agent; and means 8260 for
processing results of the first input and the second input. In one
embodiment 8230 the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment 8240 the administering one or more frozen particle
compositions (or frozen piercing implements) includes administering
the one or more frozen particle compositions (or frozen piercing
implements) to at least one substrate. In one embodiment 8250 the
at least one substrate includes one or more of a cell, tissue,
organ, structure, or device. In one embodiment 8270 means for
processing results of the first input and the second input include
means for electronically processing results of the first input and
the second input. In one embodiment 8280 means for electronically
processing results of the first input and the second input by
utilizing one or more of Gaussian smoothing, scaling, homorphic
filtering, parametric estimation techniques, Boolean operations,
Monte Carlo simulations, wavelet based techniques, mirroring,
smoothing, gradient weighted partial differential equation
smoothing, NURBS, polygonal modeling, splines and patches modeling,
algorithmic execution, logical decision-making, result prediction,
Finite Element Analysis, or modification of a CAD design.
As indicated in FIG. 83, the first input 8310 includes one or more
values related to the at least one characteristic of at least one
biological tissue. In one embodiment 8320, the first input includes
one or more spatial addresses associated with the at least one
characteristic of at least one biological tissue. In one embodiment
8330, the first input includes one or more of x, y, or z
coordinates associated with the at least one characteristic of at
least one biological tissue.
In one embodiment, the at least one characteristic 8340 of at least
one biological tissue to be at least partially constructed or at
least partially reconstructed includes one or more of:
morphological feature, anatomical feature, histological feature,
tissue hierarchical level, scaffold feature, vascular structure
feature, heterogenous tissue feature, mechanical feature,
volumetric feature, geometric feature, volumetric representation,
mechanical feature, deformation, kinematic feature, surface contour
feature, cytometric feature, cell aggregation, cell growth,
cell-cell interaction, cell-tissue interaction, biomimetic design,
cell pattern, cell deposition, organ hierarchical level, tissue
microstructure, cellular microstructure, cell junction feature,
tissue junction feature, cell-tissue classification, hard tissue
classification, soft tissue classification, tumor diagnosis, or
other feature.
In one embodiment, the at least one characteristic 8350 of at least
one biological tissue includes one or more of cellular type,
cellular function, cellular size, cellular constitution, cellular
architecture, cellular durability, cellular source, tissue type,
tissue constitution, tissue size, tissue shape, tissue function,
tissue architecture, tissue source, tissue durability, organ type,
organ constitution, organ size, organ shape, organ function, organ
architecture, organ source, or organ durability. In one embodiment,
the first input 8360 includes one or more temporal addresses
associated with the at least one characteristic of at least one
biological tissue.
As indicated in FIG. 84, in one embodiment 8410, the first input
includes one or more values derived from at least one image of the
at least one biological tissue. In one embodiment 8420, the at
least one image includes one or more images acquired by one or more
of optical coherence tomography, computer-assisted tomography scan,
computed tomography, magnetic resonance imaging, positron-emission
tomography scan, ultrasound, x-ray, laser, holography, x-ray
crystallography, electrical-impedance monitoring, microscopy,
spectrometry, flow cytommetry, radioisotope imaging, thermal
imaging, multiphoton calcium-imaging, photography, or in silico
generation.
In one embodiment 8430, the at least one biological tissue is
located in at least one of in situ, in vitro, in vivo, in utero, in
planta, in silico, or ex vivo. In one embodiment 8440, the at least
one biological tissue is at least partially located in at least one
subject. In one embodiment 8450, the system further comprises means
for accepting a third input associated with at least one feature of
the at least one subject. In one embodiment 8460, the at least one
feature of the at least one subject includes one or more of age,
gender, genotype, phenotype, proteomic profile, or health
condition.
As indicated in FIGS. 85-86, in one embodiment 8510 the means for
processing results of the first input and the second input include
means for determining at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue with one or more frozen particle compositions (or
frozen piercing implements) from one or more values derived from at
least one image of the at least one biological tissue. In one
embodiment 8520, the second input includes one or more values
related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue by administering one or more frozen particle
compositions (or frozen piercing implements) to the at least one
substrate. In one embodiment 8530, the one or more values related
to the at least one parameter of constructing or reconstructing the
at least one biological tissue includes one or more predictive
values.
In one embodiment 8540, the at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue includes one or more of porosity of the
at least one substrate, pore size of the at least one substrate,
interconnectivity of the pores of the at least one substrate,
transport properties of the at least one substrate, cell-tissue
formation of the at least one substrate, mechanical strength of the
at least one substrate, ability for attachment or distribution of
the at least one agent included in the one or more frozen particle
compositions (or frozen piercing implements) to the at least one
substrate, ability for attachment or distribution of one or more
cells or tissues to the at least one substrate, facilitation of at
least one nutrient, or tissue formation or tissue growth associated
with the at least one substrate.
In one embodiment 8610, the at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) includes one
or more of: design of plot or model for administration of one or
more frozen particle compositions (or frozen piercing implements),
constitution of the one or more frozen particle compositions (or
frozen piercing implements), formulation of the one or more frozen
particle compositions (or frozen piercing implements), size of the
one or more frozen particle compositions (or frozen piercing
implements), shape of the one or more frozen particle compositions
(or frozen piercing implements), angle of administration of the one
or more frozen particle compositions (or frozen piercing
implements), velocity of administration of the one or more frozen
particle compositions (or frozen piercing implements), quantity of
frozen particle compositions (or frozen piercing implements)
administered, rate of administration of more than one frozen
particle composition (or frozen piercing implement), spatial
location for administration of one or more frozen particle
compositions (or frozen piercing implements), temporal location for
administration of one or more frozen particle compositions (or
frozen piercing implements), method of administration of one or
more frozen particle compositions (or frozen piercing implements),
timing of administration of one or more frozen particle
compositions (or frozen piercing implements), modulation of
administration of one or more frozen particle compositions (or
frozen piercing implements), deposition of one or more frozen
particle compositions (or frozen piercing implements), or rate of
deposition of at least one agent.
In one embodiment 8620, the at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) includes at
least one parameter relating to at least partially ablating or at
least partially abrading one or more surfaces of the at least one
biological tissue with the one or more frozen particle compositions
(or frozen piercing implements).
In one embodiment 8630, the at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements) includes at
least one parameter relating to administering at least one of a
therapeutic agent, adhesive agent, biological remodeling agent,
reinforcement agent, abrasive, or explosive material with the one
or more frozen particle compositions (or frozen piercing
implements).
In one embodiment 8640, the spatial location for administration of
one or more frozen particle compositions (or frozen piercing
implements) includes one or more of x, y, or z coordinates. In one
embodiment 8650, the means for processing results include means for
comparing at least one value related to the first input associated
with the at least one characteristic of at least one biological
tissue to be at least partially constructed or at least partially
reconstructed with at least one value related to at least one image
of a target biological tissue. In one embodiment 8660, the image of
a target biological tissue includes an image of a similar
biological tissue, or an image of a dissimilar biological
tissue.
As indicated in FIG. 87, the means 8710 for processing results
include means for comparing at least one value related to the
second input associated with the at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue with at least one value related to
another administration of one or more frozen particle compositions
(or frozen piercing implements). In one embodiment 8720, the means
for processing results include means for determining one or more
differences in at least one value related to the first input and at
least one value related to at least one image of the at least one
biological tissue or a similar biological tissue. In one embodiment
8730, the means for processing results include means for
determining one or more differences in at least one value related
to the second input associated with the at least one parameter of
at least partially constructing or at least partially
reconstructing the at least one biological tissue and at least one
value related to another administration of one or more frozen
particle compositions (or frozen piercing implements) to the at
least one substrate.
In one embodiment 8740, the means for processing results include
means for generating one or more protocols for administering the
one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 8750, the means for processing
results include generating one or more blueprints for administering
the one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 8760, the one or more blueprints
include at least one of a two-dimensional plot or a
three-dimensional model. In one embodiment 8770, the one or more
blueprints include at least one representation of at least one of
organ anatomy, morphology, tissue heterogeneity, scale of vascular
system, geometry, internal architecture of an organ or tissue,
internal or external boundary distinction of a tissue or organ,
topology, or tomography.
As indicated in FIG. 88, the means for processing results include:
means for comparing one or more values related to the one or more
characteristics of the at least one biological tissue that are
determined at two or more different times to obtain one or more
characteristic comparisons; means for comparing one or more values
related to the at least one parameter of at least partially
constructing or at least partially reconstructing the at least one
biological tissue at two or more different times to obtain one or
more parameter comparisons; means for comparing the one or more
characteristic comparisons with the one or more parameter
comparisons to obtain one or more
characteristic-characteristic/parameter-parameter comparisons; and
means for comparing the one or more
characteristic-characteristic/parameter-parameter comparisons to
one or more substantially similar results obtained for one or more
other at least partially constructed or at least partially
reconstructed biological tissues. In one embodiment 8820, the
administering one or more frozen particle compositions (or frozen
piercing implements) includes depositing the at least one agent on
the at least one substrate.
As indicated in FIG. 89, the system further comprises means 8910
for displaying results of the processing. In one embodiment 8920,
the means for displaying the results of the processing include
means for displaying the results on one or more active displays. In
one embodiment 8930, the means for displaying results of the
processing include means for displaying the results on one or more
passive displays. In one embodiment 8940, the means for displaying
results of the processing includes means for displaying the results
of the processing in at least one of numeric format, graphical
format, or audio format.
In one embodiment 8950, the means for displaying results of the
processing include means for displaying a comparison of at least
one biological tissue that has been at least partially constructed
or at least partially reconstructed. In one embodiment 8960, the
means for displaying results of the processing include means for
displaying a comparison of at least one subject with one or more
other subjects. In one embodiment 8970, the means for displaying
results of the processing include means for displaying one or more
differences in the comparison of at least one value related to the
first input and at least one value related to at least one image of
a biological tissue. In one embodiment 8980, the means for
displaying results of the processing include means for displaying
one or more differences in the comparison of at least one value
related to the second input and at least one value related to
another administration of one or more frozen particle compositions
(or frozen piercing implements).
As indicated in FIG. 90, the system further comprises means 9010
for transmitting one or more signals that include information
related to the processing results of the first input and the second
input. In one embodiment 9020, the means for transmitting one or
more signals include means for transmitting one or more signals
associated with selection of one or more frozen particle
compositions (or frozen piercing implements) for administration. In
one embodiment 9030, the means for transmitting one or more signals
include means for transmitting one or more signals associated with
selection of one or more of a biological remodeling agent, adhesive
agent, abrasive, therapeutic agent, reinforcement agent, or
explosive material associated with the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
9040, the means for transmitting one or more signals include means
for transmitting one or more signals associated with comparing the
information related to the processing results of the first input
and the second input.
As indicated in FIG. 91, the one or more frozen particle
compositions (or frozen piercing implements) 9110 include one or
more frozen particles including at least one of: hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 9120, the at least one agent includes one or more
of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 9130, at least one of the adhesive agent,
therapeutic agent, reinforcement agent, abrasive, explosive
material, or biological remodeling agent is substantially in the
form of at least one of an organic or inorganic small molecule,
clathrate or caged compound, protocell, coacervate, microsphere,
Janus particle, proteinoid, laminate, helical rod, liposome,
macroscopic tube, niosome, sphingosome, toroid, vesicular tube,
vesicle, small unilamellar vesicle, large unilamellar vesicle,
large multilamellar vesicle, multivesicular vesicle, lipid layer,
lipid bilayer, micelle, organelle, cell, membrane, nucleic acid,
peptide, polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
As indicated in FIG. 92, the one or more explosive materials 9210
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 9220, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or
gelatin.
In at least one embodiment 9230, the one or more reinforcement
agents include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
As indicated in FIG. 93, the therapeutic agent 9310 includes at
least one of an anti-tumor agent, antimicrobial agent, anti-viral
agent, analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
In one embodiment 9320 the at least one biological remodeling agent
includes one or more of a blood cell, chondrocyte, endothelial
cell, hepatocyte, keratinocyte, myocyte, osteoblast, osteoclast,
osteocyte, mesenchymal cell, stem cell, progenitor cell, or
fibroblast. In one embodiment 9330, the at least one biological
remodeling agent includes one or more of calcium phosphate,
albumin, cytokine, pegylated cytokine, bone, cartilage, globulin,
fibrin, thrombin, glutaraldehyde-crosslinked pericardium, hide
powder, hyaluronic acid, hydroxylapatite, keratin, ligament,
nitinol, nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 9340, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 9350, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIGS. 94-96, a system 9400 comprises means 9410 for
accepting input associated with at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements); means 9420
for administering one or more frozen particle compositions (or
frozen piercing implements) including at least one agent; wherein
9430 the at least one agent includes one or more of a biological
remodeling agent, therapeutic agent, reinforcement agent, explosive
material, abrasive, or adhesive agent; means 9440 for evaluating
the at least one biological tissue for one or more indicators
related to deposition of at least one agent, tissue formation, or
tissue growth; and means 9610 for transmitting one or more signals
that include information related to the accepting input and
information related to the evaluating the at least one biological
tissue.
In one embodiment 9450, the means for evaluating at least one
biological tissue for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one biological tissue prior to, during, or subsequent to at least
one administration of the one or more frozen particle compositions
(or frozen piercing implements). In one embodiment 9460, the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay.
In one embodiment 9520, the image includes at least one image
acquired by one or more of optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, x-ray crystallography, laser, holography,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation. In one
embodiment 9530, the one or more indicators of tissue formation or
growth include at least one of cell migration, cell attachment,
cell retention, cell differentiation, cell proliferation,
apoptosis, diffusion of materials, angiogenesis, nucleic acid
expression, protein translation, protein modification, carbohydrate
production, carbohydrate secretion, fat production, fat secretion,
or protein secretion.
In one embodiment 9540, the input associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue by administering
one or more frozen particle compositions (or frozen piercing
implements) includes one or more of: constitution of the one or
more frozen particle compositions (or frozen piercing implements),
formulation of the one or more frozen particle compositions (or
frozen piercing implements), size of the one or more frozen
particle compositions (or frozen piercing implements), shape of the
one or more frozen particle compositions (or frozen piercing
implements), angle of administration of the one or more frozen
particle compositions (or frozen piercing implements), velocity of
administration of the one or more frozen particle compositions (or
frozen piercing implements), quantity of frozen particle
compositions (or frozen piercing implements) administered, rate of
administration of more than one frozen particle composition (or
frozen piercing implement), spatial location for administration of
one or more frozen particle compositions (or frozen piercing
implements), temporal location for administration of one or more
frozen particle compositions (or frozen piercing implements),
method of administration of one or more frozen particle
compositions (or frozen piercing implements), timing of
administration of one or more frozen particle compositions (or
frozen piercing implements), modulation of administration of one or
more frozen particle compositions (or frozen piercing implements),
deposition of one or more frozen particle compositions (or frozen
piercing implements), or rate of deposition of at least one
agent.
In one embodiment 9620, the means for transmitting one or more
signals include means for transmitting one or more signals
associated with selection of one or more frozen particle
compositions for administration. In one embodiment 9630, the means
for transmitting one or more signals include means for transmitting
one or more signals associated with selection of one or more of a
biological remodeling agent, adhesive agent, abrasive, therapeutic
agent, reinforcement agent, or explosive material associated with
the one or more frozen particle compositions(or frozen piercing
implements). In one embodiment 9640, the means for administering
one or more frozen particle compositions (or frozen piercing
implements) include means for administering the one or more frozen
particle compositions (or frozen piercing implements) to at least
one substrate. In one embodiment 9650, the at least one substrate
includes one or more of a cell, tissue, organ, structure, or
device. In one embodiment 9660, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
As indicated in FIG. 97, the at least one agent 9710 includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 9720, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent is substantially in the form of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer.
In one embodiment 9730, the one or more explosive materials include
at least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal. In one
embodiment 9740, the at least one adhesive agent includes one or
more of an acrylic polymer or copolymer, acrylamide polymer or
copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
As indicated in FIG. 98, the one or more reinforcement agents 9810
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 9820, the therapeutic agent includes at least one
of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 9830, the at least
one biological remodeling agent includes one or more of a blood
cell, chondrocyte, endothelial cell, hepatocyte, keratinocyte,
myocyte, osteoblast, osteoclast, osteocyte, mesenchymal cell, stem
cell, progenitor cell, or fibroblast.
In one embodiment 9840, the at least one biological remodeling
agent includes one or more of calcium phosphate, albumin, cytokine,
pegylated cytokine, bone, cartilage, globulin, fibrin, thrombin,
glutaraldehyde-crosslinked pericardium, hide powder, hyaluronic
acid, hydroxylapatite, keratin, ligament, nitinol, nucleic acid
polymers, polyethylene, polylethylene glycol, polyethylene glycol
diacrylate, polyethylene terephthalate fiber, polyglycol,
polylactate, polytetrafluoroethylene, polylactic acid, polyglycolic
acid, polycaprolactone, PURAMATRIX.TM. self-assembly peptide
hydrogel fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, silicone, polyurethane,
ceramic powder, elastin, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or
gelatin.
In one embodiment 9850, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, Type X collagen, elastin
fibers, or soluble elastin.
As indicated in FIG. 99, a system 9900 comprises means 9910 for
receiving one or more signals that include information related to
accepting input associated with at least one parameter of at least
partially constructing or at least partially reconstructing the at
least one biological tissue by administering one or more frozen
particle compositions (or frozen piercing implements); means 9920
for receiving one or more signals that include information related
to evaluating the at least one biological tissue for one or more
indicators of tissue formation or growth; and means for 9930
processing the information related to the input associated with at
least one parameter of at least partially constructing or at least
partially reconstructing the at least one biological tissue and the
information related to the evaluating the at least one biological
tissue. In one embodiment 9940, the evaluating at least one
biological tissue for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one biological tissue prior to, during, or subsequent to at least
one administration of one or more frozen particle compositions (or
frozen piercing implements).
In one embodiment 9950, the assay includes at least one technique
that includes spectroscopy, microscopy, electrochemical detection,
polynucleotide detection, histological examination, biopsy
analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 9960, the image includes at
least one image acquired by one or more of optical coherence
tomography, computer-assisted tomography scan, computed tomography,
laser, holography, x-ray crystallography, magnetic resonance
imaging, positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, multiphoton
calcium-imaging, photography, or in silico generation.
As indicated in FIG. 100, the one or more indicators 10010 of
tissue formation or growth include at least one of: cell migration,
cell attachment, cell retention, cell differentiation, cell
proliferation, apoptosis, diffusion of materials, angiogenesis,
nucleic acid expression, protein translation, protein modification,
carbohydrate production, carbohydrate secretion, fat production,
fat secretion, or protein secretion.
In one embodiment 10020, the input associated with at least one
parameter of at least partially constructing or at least partially
reconstructing the at least one biological tissue includes one or
more of: constitution of the one or more frozen particle
compositions (or frozen piercing implements), formulation of the
one or more frozen particle compositions (or frozen piercing
implements), size of the one or more frozen particle compositions
(or frozen piercing implements), shape of the one or more frozen
particle compositions (or frozen piercing implements), angle of
administration of the one or more frozen particle compositions (or
frozen piercing implements), velocity of administration of the one
or more frozen particle compositions (or frozen piercing
implements), quantity of frozen particle compositions (or frozen
piercing implements) administered, rate of administration of more
than one frozen particle composition (or frozen piercing
implement), spatial location for administration of one or more
frozen particle compositions (or frozen piercing implements),
temporal location for administration of one or more frozen particle
compositions (or frozen piercing implements), method of
administration of one or more frozen particle compositions (or
frozen piercing implements), timing of administration of one or
more frozen particle compositions (or frozen piercing implements),
modulation of administration of one or more frozen particle
compositions (or frozen piercing implements), deposition of one or
more frozen particle compositions (or frozen piercing implements),
or rate of deposition of at least one agent.
In one embodiment 10030, the means for receiving one or more
signals include means for receiving one or more signals associated
with selection of one or more frozen particle compositions (or
frozen piercing implements) for administration. In one embodiment
10040, the means for receiving one or more signals include means
for receiving one or more signals associated with the selection of
at least one of a biological remodeling agent, adhesive agent,
abrasive, therapeutic agent, reinforcement agent, or explosive
material associated with the one or more frozen particle
compositions (or frozen piercing implements).
As indicated in FIG. 101, in one embodiment 10110, the means for
administering one or more frozen particle compositions (or frozen
piercing implements) include means for administering the one or
more frozen particle compositions (or frozen piercing implements)
to at least one substrate. In one embodiment 10120, the at least
one substrate includes one or more of a cell, tissue, organ,
structure, or device. In one embodiment 10130, the one or more
frozen particle compositions (or frozen piercing implements)
include one or more frozen particles including at least one of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 10140, the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 10150, the adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent is substantially in the form of at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, oligosaccharide, polysaccharide, glycopeptide, glycolipid,
sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan,
lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, cell
nucleus, acid, base, buffer, protic solvent, aprotic solvent,
nitric oxide, nitric oxide synthase, nitrous oxide, amino acid,
micelle, polymer, bone cement, copolymer, cell receptor, adhesion
molecule, cytokine, chemokine, immunoglobulin, antibody, antigen,
platelet, extracellular matrix, blood, plasma, cell ligand,
zwitterionic material, cationic material, oligonucleotide,
nanotube, or piloxymer.
As indicated in FIG. 102, the one or more explosive materials 10210
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal. In one embodiment 10220, the at least one adhesive
agent includes one or more of an acrylic polymer or copolymer,
acrylamide polymer or copolymer polymer or copolymer, acrylamide
polymer or copolymer, polyacrylic acid, epoxy, urethane, gum
arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid),
polyglycolide, polylactic acid, polyether, polyol,
polyvinylpyrrolidone, pyroxylin,
polymethylacrylate-isobutene-monoisopropylmaleate, siloxane
polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate,
poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate,
polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone),
sialyl Lewis.sup.x, heme group, hemoglobin, healon,
carboxymethylcellulose, hydroxyapatite, silicone, cadherin,
integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte,
cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl
cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate,
butyl-2-cyanoacrylate, methyl 2-cyanoacrylate,
polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen,
hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon,
collagen, glycosaminoglycan, selectin, polyurethane, methacrylate,
or polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone,
silicone, albumin, glutaraldehyde, polyethylene glycol, or gelatin.
In one embodiment 10230, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 10240, the therapeutic agent includes at least
one of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof.
As indicated in FIG. 103, in one embodiment 10310, the at least one
biological remodeling agent includes one or more of a blood cell,
chondrocyte, endothelial cell, hepatocyte, keratinocyte, myocyte,
osteoblast, osteoclast, osteocyte, mesenchymal cell, stem cell,
progenitor cell, or fibroblast. In one embodiment 10320, the at
least one biological remodeling agent includes one or more of
calcium phosphate, albumin, cytokine, pegylated cytokine, bone,
cartilage, globulin, fibrin, thrombin, glutaraldehyde-crosslinked
pericardium, hide powder, hyaluronic acid, hydroxylapatite,
keratin, ligament, nitinol, nucleic acid polymers, polyethylene,
polylethylene glycol, polyethylene glycol diacrylate, polyethylene
terephthalate fiber, polyglycol, polylactate,
polytetrafluoroethylene, polylactic acid, polyglycolic acid,
polycaprolactone, PURAMATRIX.TM. self-assembly peptide hydrogel
fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, silicone, polyurethane,
ceramic powder, elastin, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or gelatin.
In one embodiment 10330, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, Type X collagen, elastin
fibers, or soluble elastin.
In one embodiment 10340, the at least one biological remodeling
agent is included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIG. 104, a system 10400 comprises means for
comparing information 10410 regarding at least one parameter for at
least partially constructing or at least partially reconstructing
at least one biological tissue of a subject by administering one or
more frozen particle compositions (or frozen piercing implements)
to the at least one subject and information regarding at least one
clinical outcome following receipt by the at least one subject of
one or more frozen particle compositions (or frozen piercing
implements); and means for providing output information 10420. In
one embodiment 10430, the output information is based on the
comparison. In one embodiment 10440, the system further comprises
means for determining at least one statistical correlation. In one
embodiment 10450, the system further comprises means for counting
the occurrence of at least one clinical outcome. In one embodiment
10460, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding quantity of cells or tissue at least partially
constructed or at least partially reconstructed. In one embodiment
10470, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding at least one cellular or tissue source. In one embodiment
10480, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of a subject includes information
regarding at least one abnormal cellular or tissue source. In one
embodiment 10490, the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of a subject includes
information regarding at least one type of cell or tissue.
As indicated in FIG. 105, the at least one agent 10510 includes at
least one agent including at least one adhesive agent, abrasive,
reinforcement agent, therapeutic agent, biological remodeling
agent, or explosive material. In one embodiment 10520, the
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of a subject includes information regarding at
least one dimension of at least one agent deposited. In one
embodiment 10530, the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
subject includes information regarding at least one dimension of at
least one depth, width, or breadth of cellular, tissue, or other
material removal or destruction. In one embodiment 10540, the
information regarding at least one clinical outcome following
receipt by the at least one subject of one or more frozen particle
compositions (or frozen piercing implements) includes information
regarding two or more subjects with one or more common
attributes.
In one embodiment 10550, the one or more common attributes include
one or more of genetic attributes, mental attributes, proteomic
attributes, phenotypic attributes, or psychological attributes. In
one embodiment 10560, the one or more common attributes include one
or more of height, weight, medical diagnosis, familial background,
results on one or more medical tests, ethnic background, body mass
index, age, presence or absence of at least one disease or
condition, species, ethnicity, race, allergies, gender, thickness
of tissue, blood vessel condition, hair or fur condition, skin
condition, tissue condition, muscle condition, organ condition,
nerve condition, brain condition, presence or absence of at least
one biological, chemical, or therapeutic agent in the subject,
pregnancy status, lactation status, genetic profile, proteomic
profile, partial or whole genetic sequence, partial or whole
proteomic sequence, medical condition, medical history, or blood
condition.
As indicated in FIG. 106, the output information 10610 includes at
least one of a response signal, comparison code, comparison plot,
diagnostic code, treatment code, test code, code indicative of at
least one treatment received, code indicative of at least one
prescribed treatment step, code indicative of at least one
vaccination administered, code indicative of at least one
therapeutic agent administered, code indicative of at least one
diagnostic agent administered, code indicative of at least one
interaction of an administered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispertion or location of at least one administered agent; code
indicative of at least one detection material administered; code
indicative of the depth of penetration of an administered agent,
code indicative of the depth of deposition of an administered
agent, or a code indicative of the condition of at least one
location of an administered frozen particle composition (or frozen
piercing implement).
In one embodiment 10620, receipt by the at least one subject of one
or more frozen particle compositions (or frozen piercing
implements) is pursuant to at least one clinical trial. In one
embodiment 10630, the method further comprises determining at least
one correlation before the administration of the one or more frozen
particle compositions (or frozen piercing implements) to the at
least one subject.
In one embodiment 10640, the method further comprises creating at
least one inclusion criterion and at least one exclusion criterion
for a clinical trial involving the one or more frozen particle
compositions (or frozen piercing implements). In one embodiment
10650, the method further comprises suggesting the inclusion of one
or more of the at least one subject in at least one clinical trial.
In one embodiment 10660, the method further comprises suggesting
the exclusion of one or more of the at least one subject in at
least one clinical trial.
As indicated in FIG. 107, the system further comprises means for
using one or more of the at least one correlation 10710 to predict
at least one clinical outcome regarding at least one second
subject. In one embodiment 10720, the at least one second subject
has not received the one or more frozen particle compositions (or
frozen piercing implements). In one embodiment 10730, the system
further comprises means for predicting at least one clinical
outcome involving the at least one second subject, wherein the at
least one second subject is a plurality of people; and means for
segregating subject identifiers associated with the plurality of
people in reference to the predicted at least one clinical outcome.
In one embodiment 10740, the system further comprises means for
determining the eligibility of the at least one second subject for
the at least one clinical trial.
In one embodiment 10750, the one or more frozen particle
compositions (or frozen piercing implements) include one or more
frozen particles including at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
As indicated in FIG. 108, the at least one agent 10810 includes one
or more of an adhesive agent, therapeutic agent, reinforcement
agent, abrasive, explosive material, or biological remodeling
agent. In one embodiment 10820, the adhesive agent, therapeutic
agent, reinforcement agent, abrasive, explosive material, or
biological remodeling agent is substantially in the form of at
least one of an organic or inorganic small molecule, clathrate or
caged compound, protocell, coacervate, microsphere, Janus particle,
proteinoid, laminate, helical rod, liposome, macroscopic tube,
niosome, sphingosome, toroid, vesicular tube, vesicle, small
unilamellar vesicle, large unilamellar vesicle, large multilamellar
vesicle, multivesicular vesicle, lipid layer, lipid bilayer,
micelle, organelle, cell, membrane, nucleic acid, peptide,
polypeptide, protein, oligosaccharide, polysaccharide,
glycopeptide, glycolipid, sphingolipid, glycosphingolipid,
glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein,
proteoglycan, chromosome, cell nucleus, acid, base, buffer, protic
solvent, aprotic solvent, nitric oxide, nitric oxide synthase,
nitrous oxide, amino acid, micelle, polymer, bone cement,
copolymer, cell receptor, adhesion molecule, cytokine, chemokine,
immunoglobulin, antibody, antigen, platelet, extracellular matrix,
blood, plasma, cell ligand, zwitterionic material, cationic
material, oligonucleotide, nanotube, or piloxymer. In one
embodiment 10830, the one or more explosive materials include at
least one of a carbonate, carbon dioxide, nitroglycerine, acid,
base, epoxy, acrylic polymer or copolymer, acrylamide polymer or
copolymer, urethane, hypoxyapatite, or reactive metal. In one
embodiment 10840, the at least one adhesive agent includes one or
more of an acrylic polymer or copolymer, acrylamide polymer or
copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
As indicated in FIG. 109, the one or more reinforcement agents
10910 include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral
matter.
In one embodiment 10920, the therapeutic agent includes at least
one of an anti-tumor agent, antimicrobial agent, anti-viral agent,
analgesic, antiseptic, anesthetic, diagnostic agent,
anti-inflammatory agent, vaccine, cell growth inhibitor, cell
growth promoter, immunogen, antigen, radioactive agent, apoptosis
promoting factor, enzymatic agent, angiogenic factor,
anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical,
cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage,
prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell
activator, epinephrine, adrenaline, neurotoxin, neuro-muscular
toxin, Botulinum toxin type A, microbial cell or component thereof,
or virus or component thereof. In one embodiment 10930, the at
least one biological remodeling agent includes one or more of a
blood cell, chondrocyte, endothelial cell, hepatocyte,
keratinocyte, myocyte, osteoblast, osteoclast, osteocyte,
mesenchymal cell, stem cell, progenitor cell, or fibroblast.
As indicated in FIG. 110, the at least one biological remodeling
agent 11010 includes one or more of calcium phosphate, albumin,
cytokine, pegylated cytokine, bone, cartilage, globulin, fibrin,
thrombin, glutaraldehyde-crosslinked pericardium, hide powder,
hyaluronic acid, hydroxylapatite, keratin, ligament, nitinol,
nucleic acid polymers, polyethylene, polylethylene glycol,
polyethylene glycol diacrylate, polyethylene terephthalate fiber,
polyglycol, polylactate, polytetrafluoroethylene, polylactic acid,
polyglycolic acid, polycaprolactone, PURAMATRIX.TM. self-assembly
peptide hydrogel fibers, linear aliphatic polyester, tendon,
fibrinogen, hyaluronate, chitin, chitosan, methylcellulose,
alginate, hyaluronic acid, agarose, cellulose, polyaldehyde
gluronate, Factor XIII, Factor XII, silk, nylon, collagen,
silicone, polyurethane, ceramic powder, elastin, pectin, wax,
glycosaminoglycan, poly(.alpha.-hydroxyacid), selectin,
glutaraldehyde, hydrophobic non-glycosylated protein, hydrogel,
peptide hydrogel, or gelatin. In one embodiment 11020, the at least
one biological remodeling agent includes one or more of Type I
collagen, Type II collagen, Type III collagen, Type VII collagen,
Type X collagen, elastin fibers, or soluble elastin. In one
embodiment 11030, the at least one biological remodeling agent is
included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As indicated in FIGS. 111-113, one embodiment relates to a system
11100 comprising means for predicting a clinical outcome of one or
more frozen particle composition (or frozen piercing implement)
treatments for at least one first subject, including means 11120
for determining a similarity or a dissimilarity in information
regarding at least one parameter for at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one first subject by administering
one or more frozen particle compositions (or frozen piercing
implements) to the at least one first subject with information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one second subject; wherein 11130 the at least one
second subject attained a clinical outcome following receipt of the
one or more frozen particle compositions (or frozen piercing
implements); and 11140 means for providing output information. In
one embodiment 11150, the output information is based on the
determination.
In one embodiment 11160, the information regarding at least one
parameter of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
second subject includes information regarding quantity of cells or
tissue at least partially constructed or at least partially
reconstructed. In one embodiment 11170, the information regarding
at least one parameter of at least partially constructing or at
least partially reconstructing at least one biological tissue of at
least one first subject includes information regarding at least one
cellular or tissue source. In one embodiment 11180, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one first subject includes information regarding at
least one abnormal cellular or tissue source.
As indicated in FIG. 112, in one embodiment 11210, the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one first subject includes information regarding at
least one type of cell or tissue. In one embodiment 11220 the
information regarding at least one parameter of at least partially
constructing or at least partially reconstructing at least one
biological tissue of at least one second subject includes
information regarding at least one type of cell or tissue. In one
embodiment 11230 the at least one agent includes one or more of an
adhesive agent, abrasive, reinforcement agent, therapeutic agent,
biological remodeling agent, or explosive material. In one
embodiment 11240 the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one first
subject includes information regarding at least one dimension of at
least one agent deposited. In one embodiment 11250 the information
regarding at least one parameter of at least partially constructing
or at least partially reconstructing at least one biological tissue
of at least one second subject includes information regarding at
least one dimension of at least one agent deposited. In one
embodiment 11260, the information regarding at least one parameter
of at least partially constructing or at least partially
reconstructing at least one biological tissue of at least one
second subject includes information regarding at least one
dimension of at least one depth, width, or breadth of cellular,
tissue, or other material removal or destruction. In one embodiment
11270, the information regarding at least one parameter of at least
partially constructing or at least partially reconstructing at
least one biological tissue of at least one first subject includes
information regarding at least one dimension of at least one depth,
width, or breadth of cellular, tissue, or other material removal or
destruction.
As indicated in FIG. 113, in one embodiment 11310, the information
regarding at least one clinical outcome following receipt by the at
least one second subject of one or more frozen particle
compositions (or frozen piercing implements) includes information
regarding two or more subjects with one or more common attributes.
In one embodiment 11320, the one or more common attributes include
but are not limited to genetic attributes, mental attributes,
proteomic attributes, phenotypic attributes, or psychological
attributes. In one embodiment 11330, the one or more common
attributes include at least one of height; weight; medical
diagnosis; familial background; results on one or more medical
tests; ethnic background; body mass index; age; presence or absence
of at least one disease or condition; species; ethnicity; race;
allergies; gender; thickness of epidermis; thickness of dermis;
thickness of stratum corneum; keratin deposition; collagen
deposition; blood vessel condition; skin condition; hair or fur
condition; muscle condition; tissue condition; organ condition;
nerve condition; brain condition; presence or absence of at least
one biological, chemical, or therapeutic agent in the subject;
pregnancy status; lactation status; medical history; genetic
profile; proteomic profile; partial or whole genetic sequence;
partial or whole proteomic sequence; lymph condition, medical
history, or blood condition.
In one embodiment 11340, the output information includes at least
one of a response signal, a comparison code, a comparison plot, a
diagnostic code, a treatment code, a test code, a code indicative
of at least one treatment received, a code indicative of at least
one prescribed treatment step, a code indicative of at least one
vaccination delivered; a code indicative of at least one
therapeutic agent delivered; a code indicative of at least one
diagnostic agent delivered; a code indicative of at least one
interaction of a delivered agent and at least one biological or
chemical agent in the subject; a code indicative of at least one
dispersion or location of at least one delivered agent; a code
indicative of at least one detection material delivered; a code
indicative of the depth of penetration of a delivered agent; or a
code indicative of the condition of at least one location of a
delivered or administered frozen particle composition (or frozen
piercing implement) 2700.
As indicated in FIG. 114, in one embodiment 11410, receipt by the
at least one second subject of one or more frozen particle
compositions (or frozen piercing implements) is pursuant to at
least one clinical trial. In one embodiment 11420, the system
further comprises means for determining at least one correlation
before the administration of the one or more frozen particle
compositions (or frozen piercing implements) to the at least one
first subject. In one embodiment 11430, the system further
comprises means for creating at least one inclusion criterion and
at least one exclusion criterion for a clinical trial involving the
one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 11440, the system further comprises
means for suggesting the inclusion of one or more of the at least
one first subject in at least one clinical trial.
In one embodiment 11450, the system further comprises means for
suggesting the exclusion of one or more of the at least one first
subject in at least one clinical trial. In one embodiment 11460,
the system further comprises means for using one or more of the at
least one first subject in at least one clinical trial. In one
embodiment 11470, the at least one second subject has not received
the one or more frozen particle compositions (or frozen piercing
implements). In one embodiment 11480, the system further comprises
means for predicting at least one clinical outcome involving the at
least one second subject, wherein the at least one second subject
is a plurality of people; and means for segregating subject
identifiers associated with the plurality of people in reference to
the predicted at least one clinical outcome.
As indicated in FIG. 115, in one embodiment 11510, the one or more
frozen particle compositions (or frozen piercing implements)
include at least one of hydrogen oxide, nitrogen, oxygen, air,
helium, neon, argon, xenon, chlorine, bromine, carbon dioxide,
acetone, ethyl acetate, dimethyl sulfoxide, dimethyl formamide,
dioxane, tetrahydrofuran, acetronitrile, acetic acid, n-butanol,
isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, or
diethyl ether.
In one embodiment 11520, the one or more frozen particle
compositions (or frozen piercing implements) include one or more of
an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent.
In one embodiment 11530, the adhesive agent, therapeutic agent,
reinforcement agent, abrasive, explosive material, or biological
remodeling agent includes at least one of an organic or inorganic
small molecule, clathrate or caged compound, protocell, coacervate,
microsphere, Janus particle, proteinoid, laminate, helical rod,
liposome, macroscopic tube, niosome, sphingosome, toroid, vesicular
tube, vesicle, small unilamellar vesicle, large unilamellar
vesicle, large multilamellar vesicle, multivesicular vesicle, lipid
layer, lipid bilayer, micelle, organelle, cell, membrane, nucleic
acid, peptide, polypeptide, protein, oligosaccharide,
polysaccharide, glycopeptide, glycolipid, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, cell
nucleus, acid, base, buffer, protic solvent, aprotic solvent,
nitric oxide, nitric oxide synthase, nitrous oxide, amino acid,
micelle, polymer, bone cement, copolymer, cell receptor, adhesion
molecule, cytokine, chemokine, immunoglobulin, antibody, antigen,
platelet, extracellular matrix, blood, plasma, cell ligand,
zwitterionic material, cationic material, oligonucleotide,
nanotube, or piloxymer.
In one embodiment 11540, the one or more explosive materials
include at least one of a carbonate, carbon dioxide,
nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer,
acrylamide polymer or copolymer, urethane, hypoxyapatite, or
reactive metal.
In one embodiment 11610, the at least one adhesive agent includes
one or more of an acrylic polymer or copolymer, acrylamide polymer
or copolymer polymer or copolymer, acrylamide polymer or copolymer,
polyacrylic acid, epoxy, urethane, gum arabic, polyester,
polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide,
polylactic acid, polyether, polyol, polyvinylpyrrolidone,
pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate,
siloxane polymer, polylactic-co-glycolic-acid,
poly-3-hydroxybutyrate, poly-4-hydroxybutyrate,
polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate,
polycaprolactone, poly (e-caprolactone), sialyl Lewis.sup.x, heme
group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite,
silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte,
maleic polyelectrolyte, cellulose, resilin, cyanoacrylate,
isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate,
n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl
2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin,
fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk,
nylon, collagen, glycosaminoglycan, selectin, polyurethane,
methacrylate, or polysulfide, polyanhydride, polydioxanone,
poly-p-dioxanone, silicone, albumin, glutaraldehyde, polyethylene
glycol, or gelatin.
In one embodiment 11620, the one or more reinforcement agents
include one or more of polyaramid, vinylester matrix, metal,
ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide,
nylon, silk, rayon, acetate, modacrylic, olefin, acrylic,
polyester, aromatic polyester, poly-lactic acid, vinyon, saran,
spandex, vinalon, aromatic nylon, vinylidene chloride, modal,
polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance
polyethylene, polypyridobenzimidazole, vectran, acrylonitrile
rubber, glass, copper, iron, steel, sodium, potassium, calcium,
zinc, manganese, carbon, magnesium, silicon, silica, frozen
hydrogen oxide ice, plant matter, animal matter, or mineral matter
11630 wherein the therapeutic agent includes at least one of an
anti-tumor agent, antimicrobial agent, anti-viral agent, analgesic,
antiseptic, anesthetic, diagnostic agent, anti-inflammatory agent,
vaccine, cell growth inhibitor, cell growth promoter, immunogen,
antigen, radioactive agent, apoptosis promoting factor, enzymatic
agent, angiogenic factor, anti-angiogenic factor, hormone, vitamin,
mineral, nutraceutical, cytokine, chemokine, probiotic, coagulant,
anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer,
smooth muscle cell activator, epinephrine, adrenaline, neurotoxin,
neuro-muscular toxin, Botulinum toxin type A, microbial cell or
component thereof, or virus or component thereof.
In one embodiment 11710, the at least one biological remodeling
agent includes one or more of a blood cell, chondrocyte,
endothelial cell, hepatocyte, keratinocyte, myocyte, osteoblast,
osteoclast, osteocyte, mesenchymal cell, stem cell, progenitor
cell, or fibroblast.
In one embodiment 11720, the at least one biological remodeling
agent includes one or more of calcium phosphate, albumin, cytokine,
pegylated cytokine, bone, cartilage, globulin, fibrin, thrombin,
glutaraldehyde-crosslinked pericardium, hide powder, hyaluronic
acid, hydroxylapatite, keratin, ligament, nitinol, nucleic acid
polymers, polyethylene, polylethylene glycol, polyethylene glycol
diacrylate, polyethylene terephthalate fiber, polyglycol,
polylactate, polytetrafluoroethylene, polylactic acid, polyglycolic
acid, polycaprolactone, PURAMATRIX.TM. self-assembly peptide
hydrogel fibers, linear aliphatic polyester, tendon, fibrinogen,
hyaluronate, chitin, chitosan, methylcellulose, alginate,
hyaluronic acid, agarose, cellulose, polyaldehyde gluronate, Factor
XIII, Factor XII, silk, nylon, collagen, silicone, polyurethane,
ceramic powder, elastin, pectin, wax, glycosaminoglycan,
poly(.alpha.-hydroxyacid), selectin, glutaraldehyde, hydrophobic
non-glycosylated protein, hydrogel, peptide hydrogel, or
gelatin.
In one embodiment 11730, the at least one biological remodeling
agent includes one or more of Type I collagen, Type II collagen,
Type III collagen, Type VII collagen, Type X collagen, elastin
fibers, or soluble elastin.
In one embodiment 11740, the at least one biological remodeling
agent is included as part of a carrier that assists in synthesis or
activation of the at least one biological remodeling agent.
As illustrated in FIG. 118, a cross-section of animal skin (e.g.,
human skin, as shown) has multiple layers, including but not
limited to the stratum corneum (approximately 10-15 microns thick)
as part of the epidermis (approximately 100-150 microns thick). In
one embodiment, at least one frozen particle composition, at least
one frozen piercing implement, or at least one frozen piercing
implement device is administered to a substrate, such as skin, and
is configured to penetrate the stratum corneum or entire epidermis,
without reaching the underlying nerves (e.g., "sensory nerve ending
for touch," of FIG. 118). In one embodiment, at least one agent
(e.g., an anesthetic) is included in the at least one frozen
particle composition, at least one frozen piercing implement, or at
least one frozen piercing implement device that at least partially
disrupts nerve function in such a manner that even if further
frozen particle compositions, frozen piercing implements, or frozen
piercing implement devices are administered, pain is reduced or
eliminated regardless of the depth of penetration.
As illustrated in FIG. 119, in one embodiment, at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device is administered by propelling under a rapid
expansion force (e.g., by way of at least one outlet) which may be
the result of at least one explosion. In one embodiment, the
explosion includes flash-boiling the at least one cooling liquid.
In one embodiment, the explosion includes a boiling liquid
expanding vapor explosion (BLEVE) of the at least one cooling
liquid.
The BLEVE of the cooling liquid can be calculated according to
standard techniques. For example, in FIG. 119, a diagram of the
relationship between the pressure for a substance in various phases
of liquid and gas, and the volume occupied by that substance. See,
for example, the worldwide web at: criticalprocesses.com/BLEVE.htm,
the subject matter of which is incorporated herein by reference.
The line from point A to B indicates the substance is in liquid
form and as the volume the substance occupies expands, the pressure
falls until it reaches the vapor pressure of the liquid (B) for a
particular temperature. Id. The liquid then evaporates to become a
liquid-gas mixture, and the pressure stays constant at the vapor
pressure. Eventually the substance reaches point C, where the
liquid has been converted to gas phase, and the pressure drops with
further expansion. Id.
If the pressure falls suddenly, the substance can become unstable
liquid along the line from point B to point S. Id. S is known as a
spinodal point, and the slope of the line at this point is zero
(i.e. (.differential.p/.differential.V)=0). Id. The dotted line
connects spinodal points at different temperatures, forming the
spinodal curve, and ending at the critical point. Id. During a
BLEVE, density variations develop spontaneously and homogenously
into liquid and gas regions. Id. The rise in pressure on the vapor
pressure line from point B to C occurs rapidly, and a BLEVE
results. Id.
As illustrated in FIG. 120, for carbon dioxide, conditions for
inducing a BLEVE can be calculated for a particular substance since
the entropy of the system remains constant. Id. Thus, conditions
that induce a BLEVE for any particular substance are found along
the spinodal curve for that substance, between 1 bar and the
critical point where the curve ends. Id.
As illustrated in FIG. 121, various embodiments of frozen particle
compositions or frozen piercing implements (alone, or as part of a
device), include different sizes, shapes, or configurations. In one
embodiment (as depicted in FIG. 121A), the frozen particle
composition or frozen piercing implement includes a tip (or distal
end), a shaft, and a base (or proximal end). As indicated in FIG.
121A, the height, width, or breadth can vary according to
particular parameters for making or administering the at least one
frozen particle composition or frozen piercing implement. In one
embodiment, multiple different frozen particle compositions or
frozen piercing implements are included in a device, wherein
multiple different parameters (including but not limited to size,
shape, density, height, width, breadth, or configuration) are
included.
In one embodiment, FIG. 121B includes a frozen particle composition
or frozen piercing implement with at least one cavity. As disclosed
herein, in one embodiment, the at least one cavity includes at
least one solid, liquid, gas, or other form of substance. In one
embodiment, the at least one cavity includes at least one agent.
Various non-limiting examples of agents are described herein. In
one embodiment, the at least one frozen particle composition or
frozen piercing implement includes at least one channel. In one
embodiment, as indicated in FIG. 121B, the at least one frozen
particle composition or frozen piercing implement includes multiple
cavities. As illustrated in FIG. 121C, in one embodiment, the at
least one frozen particle composition or frozen piercing implement
includes at least one of a tapered, mushroom shaped, beveled,
serated, or other configuration (respectively from left to right in
the figure).
As illustrated in FIG. 122, strength of frozen piercing implements
is indicated by a sudden drop in force at the point of failure.
See, for example, Park et al., Ibid. The maximum force just prior
to the sudden drop defines the force of the piercing implement
failure. As shown in FIG. 122, according to the published study,
microneedles containing polylactic acid with a height of
approximately 800 .mu.m and a base diameter of approximately 200
.mu.m display a failure force of approximately 0.50 Newtons/needle,
which is approximately three times greater than the force needed
for insertion into skin. See, for example, Park et al, J. Contr.
Rel., vol. 104, pp. 51-66 (2005), which is incorporated herein by
reference.
As illustrated in FIG. 123, in one embodiment, at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device includes at least one shape or configuration
illustrated. In one embodiment, the at least one frozen particle
composition, or frozen piercing implement includes at least one
cavity or channel. For example, FIG. 123A illustrates a conical
shape, FIG. 123B illustrates a cylindrical and conical hybrid, FIG.
123C indicates another conical shape, FIG. 123D illustrates a
pyramidal shape, FIG. 123E illustrates a cuboidal and pyramidal
hybrid,
FIG. 123F illustrates a cylindrical shape, FIG. 123G illustrates
several planar rectangular shapes attached to a support structure
(e.g., for a frozen piercing implement device), and FIG. 123H
illustrates several planar triangular shapes attached to a support
structure (e.g., for a frozen piercing implement device).
As illustrated in FIG. 124, in one embodiment at least one frozen
piercing implement device 12400 includes multiple frozen piercing
implements contacting a support structure. In one embodiment, at
least one frozen piercing implement is made by contacting at least
one fluid 12420 with at least one frame 12430 defining at least one
projection, raising the at least one frame approximately vertically
from the at least one fluid, such that the surface tension of the
at least one fluid is maintained, forming at least one fluid
extension 12420 (FIGS. 124D-G); exposing the at least one fluid
extension to conditions for a time sufficient to solidify the at
least one fluid'extension 12420 (FIGS. 124D-G) in the form of at
least one frozen particle composition or frozen piercing implement.
In one embodiment, the fluid 12420 is located on at least one
support structure 12410. Subsequent to making the at least one
frozen piercing implement from the fluid extension, the implement
can remain on the support structure, or be removed.
As illustrated in FIG. 125, at least one frozen piercing implement
includes at least one functionalized surface 12560. In one
embodiment (FIG. 125 A) at least one inner surface 12550 of the at
least one frozen piercing implement 12590 is functionalized. For
example, the inner surface may include at least one carboxylic
group 12510, capable of providing a surface tending toward a
hydrophilic, or anionic surface. In one embodiment (FIG. 125 B) at
least one outer surface 12560 of the at least one frozen piercing
implement is functionalized. For example, the outer surface may
include at least one lipid group 12540, capable of providing a
surface tending toward a hydrophobic, or lipophilic surface. In one
embodiment (FIGS. 125 C and 125 D) at least one inner surface of
the at least one frozen piercing implement is functionalized. For
example, the inner surface may include at least one amino group
12585, capable of providing a surface tending toward a hydrophilic,
cationic surface. In one embodiment (FIG. 125 E) at least one
surface of the frozen piercing implement includes at least one
silane group 12595. For example, the surface may be modified to
include at least one alkoxysilane of Formula I:
(R.sup.2)Si(R.sup.1).sub.3 (Formula I), wherein R.sup.1 includes at
least one of a chlorine, acetoxy, or alkoxy, and R.sup.2 includes
at least one of an organofunctional group (e.g. methyl, phenyl,
isobutyl, octyl, --NH(CH.sub.2).sub.3NH.sub.2, epoxy, methacryl,
etc.), alkyl, aryl, amino, methacryloxy, or epoxy. In one
embodiment, the Formula I silanized surface may be capable of
imparting at least one property of nonpolar, hydrophilic,
hydrophobic, organophilic, lipophilic, lipophobic, acidic, basic,
neutral, increased or decreased permeability, or combinations
thereof. See, for example, U.S. Patent Application Publication No.
2008/0078376, which is incorporated herein by reference.
In one embodiment, the inner surface 12550 is functionalized with a
charged group 12575. In one embodiment, the underside of the
support structure 12580 is in fluid communication with at least one
compartment (not shown). In one embodiment, the topside of the
support structure 12530 can also be functionalized 12570.
In one embodiment, the at least one functionalized surface 12560
includes one or more functionalities including one or more of
charge functionality, hydrophobic functionality, hydrophilic
functionality, chemically reactive functionality, organo
functionality, or wetability. In one embodiment, the at least one
functionalized surface 12560 includes one or more functional groups
including at least one of an agent, alcohol, hydroxyl, amine,
aldehyde, dye, ketone, carbonyl, thiol, alkoxysilane, phosphate,
carboxyl, carboxylic acid, carboxylate, nucleic acid, amino acid,
polypeptide, protein, lipid, carbohydrate, metal, --NH.sub.3.sup.+,
--COOH, --COO--, --SO.sub.3, CH.sub.2N.sup.+(CH.sub.3).sub.3,
--(CH.sub.2).sub.xCH.sub.3, --C((CH.sub.2).sub.xCF.sub.3).sub.3,
--CH.sub.2N(C.sub.2H.sub.5).sub.2, --NH.sub.2,
--(CH.sub.2).sub.xCOOH, --(OCH.sub.2CH.sub.2).sub.xCH.sub.3,
--SiOH, or --OH.
In one embodiment, the at least one functionalized surface 12560
includes at least part of an outer surface. In one embodiment, the
at least one functionalized surface includes at least part of an
inner surface 12550.
As illustrated in FIG. 126, in one embodiment, at least one frozen
particle composition, frozen piercing implement, or component of a
frozen piercing implement device 12600 includes at least one distal
end, or tip, 12810, and a proximal end, or base end, 12820. In one
embodiment, the frozen particle composition or frozen piercing
implement includes at least one channel 12800. In one embodiment,
the at least one channel includes at least one inner surface 12830
and at least one outer surface 12860. In one embodiment, the frozen
particle composition or frozen piercing implement are substantially
solid in form. As indicated by FIGS. 126A through 126G, the frozen
particle compositions or frozen piercing implements can take a
variety of forms, shapes, or configurations. For example, FIGS.
126C-126D illustrate at least one frozen piercing implement
including at least one beveled end. In another example, FIG. 126G
illustrates at least one frozen piercing implement including at
least one jagged end. In another example, FIG. 126D includes at
least one frozen piercing implement including at least one blunt or
substantially flattened end. In another example, FIGS. 126A, 126B,
and 126F illustrate at least one frozen piercing implement
including at least one tapered end.
As illustrated in FIG. 127 A, in one embodiment, an array device
comprises a body portion 12720, including a support structure
having a surface 12725; and a plurality of piercing implements
12750 extending substantially outward from the support structure
12725. In one embodiment, the plurality of piercing implements
12750 includes at least one frozen piercing implement 12755. In one
embodiment, the device includes at least one compartment 12700
configured to hold at least one agent to be administered to the at
least one substrate, or at least one material extracted from the at
least one substrate. In one embodiment, at least one piercing
implement 12755 is in fluid communication with the at least one
compartment 12700, and includes a distal end opening (e.g., a port)
12740 from which at least one agent can be administered to the at
least one substrate, or at least one material can be extracted from
the at least one substrate. In one embodiment, the device includes
at least one backing member 12710, which can be a portion of the
overall support structure 12725, and can function as an outer
portion of the support structure (e.g., in at least one embodiment,
the compartment is disposable and the backing member and/or
remaining support structure is recyclable or reusable). In one
embodiment, the backing member is an outer shell. In one
embodiment, the backing member is multi-layered (e.g., polymeric or
paper-based materials). In one embodiment, a fastening mechanism
(e.g., adhesive, VELCRO.RTM., etc.) 12730 is included to attach the
device to the at least one substrate (e.g., the surface of a
subject or device, etc.). In one embodiment, the fastening
mechanism 12730 is at least temporarily covered by a device cover
12760.
In one embodiment, the plurality of sterile frozen piercing
implements 12750 have at least one major dimension of approximately
one centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween.
In one embodiment, the plurality of sterile frozen piercing
implements 12750 extends substantially perpendicular to the support
structure. In one embodiment, the plurality of sterile frozen
piercing implements 12750 extends through the surface of the
support structure 12725. In one embodiment, the plurality of
sterile frozen piercing implements 12750 extends from the surface
of the support structure 12725. In one embodiment, the support
structure 12725 includes at least one frozen composition. In one
embodiment, the support structure 12725 includes at least one
frozen composition also included in at least one frozen piercing
implement 12755. In one embodiment, the support structure 12725 is
at least partially frozen. In one embodiment, the support structure
12725 and at least one frozen piercing implement 12755 of the
plurality of frozen piercing implements 12750 include at least one
common constituent. In one embodiment, the plurality of frozen
piercing implements 12750 are positioned substantially parallel to
each other.
In one embodiment, the plurality of frozen piercing implements
12750 are positioned substantially in a predetermined spatial
pattern. In one embodiment, the predetermined spatial pattern is at
least partially periodic. See FIG. 131 for various non-limiting
examples of spatial patterns for array devices, including at least
partially periodic patterns.
In one embodiment, the plurality of frozen piercing implements
12750 includes an area density of implements greater than or
approximately equal to 1 .mu.m, greater than or approximately equal
to 10 .mu.m, greater than or approximately equal to 50 .mu.m,
greater than or approximately equal to 100 .mu.m, greater than or
approximately equal to 500 .mu.m, greater than or approximately
equal to 1 mm, greater than or approximately equal to 10 mm,
greater than or approximately equal to 50 mm, greater than or
approximately equal to 100 mm, greater than or approximately equal
to 500 mm, greater than or approximately equal to 1 cm, or any
value there between. In one embodiment, the plurality of frozen
piercing implements 12750 includes approximately the same
length.
In one embodiment, the length of a frozen piercing implement is
associated with the position or location of the frozen piercing
implement in the array device. For some non-limiting examples,
longer or taller implements may be in the center, while shorter
implements are around the periphery; longer or taller implements
may be in a particular pattern within the spatial pattern of the
array device, while shorter implements are in a different
particular pattern; implements in the center may include different
agents that extend their length (e.g. reinforcement agents); or
implements along one particular side may be longer than implements
along another particular side. In one embodiment, the length of a
frozen piercing implement is actuatable, or controllable.
In one embodiment, the at least one frozen piercing implement is
configured to be deactivated. In one embodiment, the at least one
frozen piercing implement is configured to be deactivated by at
least one component of the array device or the frozen piercing
implement. In one embodiment, the at least one frozen piercing
implement configured to be deactivated by thermal transfer to the
at least one frozen piercing implement.
In one embodiment, the plurality of frozen piercing implements
12750 is positioned as at least a portion of a fluidic or injection
device. See FIGS. 127B, 129, and 130, for various non-limiting
examples of devices.
As illustrated in FIG. 127, in one embodiment, the plurality of
frozen piercing implements 12750 is positioned in fluid
communication with at least one compartment 12700 configured to be
mechanically regulated. In one embodiment, the plurality of frozen
piercing implements 12750 is positioned on at least one surface
12725.
In one embodiment, a fluidic device comprises a support structure
12725 at least partially defining at least one compartment 12700,
and at least one frozen piercing implement 12755 in fluid
communication with the at least one compartment 12700.
In one embodiment, at least one frozen piercing implement of the
plurality of frozen piercing implements includes one or more of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment, at least one frozen piercing implement 12755 of
the plurality of frozen piercing implements 12750 is configured to
deliver at least one agent, and further comprises at least one
agent. In one embodiment, the at least one major dimension includes
at least one of the radius, diameter, length, width, height, or
perimeter.
In one embodiment, each frozen piercing implement 12755 of the
plurality 12750 includes at least one agent different than the
agent of every other frozen piercing implement of the plurality
12750. In one embodiment, at least one frozen piercing implement
12755 of the plurality 12750 includes at least two different
agents. In one embodiment, the device includes at least two
different agents. In one embodiment, the at least one agent
includes at least one antigen. In one embodiment, each frozen
piercing implement 12755 of the plurality 12750 includes at least
one antigen. In one embodiment, the at least one antigen includes
at least one allergen. In one embodiment, the frozen piercing
implement 12755 is configured for delivering the at least one
agent. Various non-limiting examples of agents are described
herein. In one embodiment, the at least one agent includes at least
one of a nontoxic, biocompatible, bioresorbable, or biodegradable
agent. In one embodiment, at least two frozen piercing implements
of the plurality of frozen piercing implements have at least one
agent in common. In one embodiment, each frozen piercing implement
12755 of the plurality of frozen piercing implements 12750 has at
least one agent in common. In one embodiment, each frozen piercing
implement 12755 of the plurality of frozen piercing implements
12750 is different from every other piercing implement by varying
one or more of: size of implement, shape of implement, or
constitution of implement.
In one embodiment, at least two frozen piercing implements of the
plurality 12750 of frozen piercing implement differ in one or more
of: size of implement, shape of implement, or constitution of
implement. In one embodiment, at least one frozen piercing
implement of the plurality of frozen piercing implements 12750
includes hydrogen oxide in one or more phases including at least
one of amorphous solid water, low density amorphous ice, high
density amorphous ice, very high density amorphous ice, clathrate
ice, hyperquenched glassy water, ice Ic, ice II, ice III, ice IV,
ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice XII,
ice XIII, ice XIV, or ice XV. In one embodiment, at least one of
the plurality of frozen piercing implements is substantially solid
at approximately 0.degree. C., approximately -10.degree. C.,
approximately -20.degree. C., approximately -30.degree. C.,
approximately -40.degree. C., approximately -50.degree. C.,
approximately -60.degree. C., approximately -70.degree. C.,
approximately -75.degree. C., approximately -80.degree. C.,
approximately -85.degree. C., approximately -90.degree. C.,
approximately -95.degree. C., approximately -100.degree. C.,
approximately -120.degree. C., approximately -150.degree. C.,
approximately -180.degree. C., approximately -200.degree. C.,
approximately -220.degree. C., approximately -250.degree. C., or
any value less than or therebetween. In one embodiment, the array
device has at least one major dimension of approximately one
centimeter or less, approximately one millimeter or less,
approximately one micrometer or less, approximately one nanometer,
or any value therebetween.
In one embodiment, the plurality of frozen piercing implements
12750 includes a two dimensional array, or a three dimensional
array. In one embodiment, the plurality of frozen piercing
implements are arranged in at least one configuration including a
regular or irregular shape. See for example, FIG. 130 for various
non-limiting examples of array device shapes. In one embodiment,
the plurality of frozen piercing implements are arranged in at
least one configuration including at least one of a rectangle,
square, circle, triangle, or polygon. See for example, FIG.
130.
In one embodiment, at least one frozen piercing implement of the
plurality 12750 of frozen piercing implements includes at least one
functionalized surface. See, for example, FIG. 125, for various
non-limiting examples of functionalized surfaces.
In one embodiment, the array device includes at least one
attachment component 12730 configured to secure the array device to
at least one substrate. In one embodiment, the at least one
attachment component 12730 includes at least one adhesive material.
In one embodiment, the device is configured to substantially form a
patch. In one embodiment, the array device further comprising at
least one compartment 12700. In one embodiment, the at least one
compartment includes, for example, at least one syringe or valve.
See, for example, FIG. 130 for various non-limiting examples of a
syringe and valve. In one embodiment, the at least one compartment
12700 is configured to hold at least one material extracted from at
least one substrate. In one embodiment, the at least one
compartment 12700 is in fluid communication with at least one
frozen piercing implement of the plurality of frozen piercing
implements. In one embodiment, the at least one compartment 12700
is configured for holding at least one agent. In one embodiment,
the at least one compartment 12700 is configured for holding at
least one cryogenic substance.
In one embodiment, the frozen piercing implement is configured to
pierce at least one substrate to a depth of approximately 1 .mu.m,
approximately 5 .mu.m, approximately 10 .mu.m, approximately 15
.mu.m, approximately 20 .mu.m, approximately 50 .mu.m,
approximately 100 .mu.m, approximately 120 .mu.m, approximately 150
.mu.m, approximately 200 .mu.m, approximately 250 .mu.m,
approximately 300 .mu.m, approximately 350 .mu.m, approximately 400
.mu.m, approximately 450 .mu.m, approximately 500 .mu.m,
approximately 600 .mu.m, approximately 700 .mu.m, approximately 800
.mu.m, approximately 900 .mu.m, approximately 1 mm, approximately 2
mm, approximately 3 mm, approximately 4 mm, approximately 5 mm, or
any value therebetween. In one embodiment, the at least one frozen
piercing implement is configured to abrade or ablate at least one
substrate surface 12895. In one embodiment, the plurality of frozen
piercing implements 12750 is positioned such that each frozen
piercing implement of the array device contacts a single cell of at
least one biological tissue. In one embodiment, at least one
implement of the plurality of frozen piercing implements includes
at least one sensor.
In one embodiment, at least one implement of the plurality of
frozen piercing implements 127500 is configured for extracting at
least one material from at least one substrate 12895. Specific
non-limiting examples of materials that are capable of being sensed
or extracted from at least one substrate are provided herein.
In one embodiment, at least one implement of the plurality of
frozen piercing implements further includes at least one of an
organic or inorganic small molecule, clathrate or caged compound,
protocell, coacervate, microsphere, Janus particle, proteinoid,
laminate, helical rod, liposome, macroscopic tube, niosome,
sphingosome, toroid, vesicular tube, vesicle, small unilamellar
vesicle, large unilamellar vesicle, large multilamellar vesicle,
multivesicular vesicle, lipid layer, lipid bilayer, micelle,
organelle, cell, membrane, nucleic acid, peptide, polypeptide,
protein, glycopeptide, glycolipid, lipoprotein, sphingolipid,
glycosphingolipid, glycoprotein, peptidoglycan, lipid,
carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus,
acid, support structure, buffer, protic solvent, aprotic solvent,
nitric oxide, nitrous oxide, nitric oxide synthase, amino acid,
micelle, polymer, copolymer, monomer, prepolymer, cell receptor,
adhesion molecule, cytokine, chemokine, immunoglobulin, antibody,
antigen, platelet, extracellular matrix, blood, plasma, cell
ligand, zwitterionic material, cationic material, oligonucleotide,
nanotube, piloxymer, transfersome, gas, element, contaminant,
radioactive particle, hormone, microorganism, bacteria, virus,
quantum dot, contrast agent, or any part thereof.
In one embodiment, the plurality of frozen piercing implements
12750 includes at least approximately 2 implements, approximately 5
implements, approximately 10 implements, approximately 20
implements, approximately 50 implements, approximately 100
implements, approximately 200 implements, approximately 300
implements, approximately 400 implements, approximately 500
implements, approximately 600 implements, approximately 700
implements, approximately 800 implements, approximately 900
implements, approximately 1000 implements, approximately 5000
implements, approximately 10000 implements, or any value
therebetween or greater.
In one embodiment, the spacing between two or more frozen piercing
implements includes at least approximately 1 nm, approximately 5
nm, approximately 10 nm, approximately 20 nm, approximately 50 nm,
approximately 80 nm, approximately 100 nm, approximately 200 nm,
approximately 300 nm, approximately 400 nm, approximately 500 nm,
approximately 600 nm, approximately 700 nm, approximately 800 nm,
approximately 900 nm, approximately 1 .mu.m, approximately 5 .mu.m,
approximately 10 .mu.m, approximately 15 .mu.m, approximately 20
.mu.m, approximately 50 .mu.m, approximately 100 .mu.m,
approximately 120 .mu.m, approximately 150 .mu.m, approximately 200
.mu.m, approximately 500 .mu.m, approximately 1 mm, approximately 5
mm, approximately 10 mm, approximately 100 mm, approximately 500
mm, approximately 1 cm, approximately 5 cm, approximately 10 cm, or
any value therebetween or greater.
As illustrated in FIG. 127 B, in on embodiment, the frozen piercing
implement includes at least one distal end 12775, at least one
frozen piercing implement shaft 12735, which may include at least
one channel 12755, or port (e.g., outlet or inlet ports at the
distal end 12765 or proximal end 12705). In one embodiment, the
device includes at least one sensor, valve, gate, transducer,
actuator, detector, heater, circuit, on-chip electronics, or other
features 12745 are located in the body of the device 12725. In one
embodiment, at least one electrode contact site 12715 serves as an
outside connection to at least one resistor 12785, which may be
utilized to form a thermally driven, cascaded bubble pump or
heater. In one embodiment, the device includes at least one
compartment 12705 configured to hold at least one agent or at least
one material extracted from at least one substrate. Such devices
may include a micro- or nano-scale, as well as larger scales.
In one embodiment, the at least one frozen piercing implement
includes at least one port (e.g., 12765, 12705). The at least one
port can be an inlet port, or an outlet port, and may vary
according to the relative use of the device. For example, in one
embodiment, a first port 12705 functions as an inlet port when
administering at least one agent to at least one substrate by way
of a second port 12765 functioning as an outlet port. In another
example, in one embodiment a first port 12765 functions as an inlet
port when extracting at least one material from at least one
substrate. In one embodiment, the at least one material is analyzed
or manipulated while still in the device (according to at least one
feature 12745), or the at least one material exits the device by
way of at least one port 12705 functioning as an outlet port. In
one embodiment, at least one outlet port is in fluid communication
with at least one inlet port.
As illustrated in FIG. 128, in one embodiment, the plurality of
implements is included in an array positioned on a support
structure 12865 that has a surface 12880. In one embodiment, the at
least one frozen piercing implement 12840 includes at least one
channel 12850 that includes at least one inner surface 12830 and at
least one outer surface 12860. In one embodiment, the frozen
piercing implement includes a distal end 12810 and a proximal end
12820. In one embodiment, the frozen piercing implement 12840
includes a channel 12850 that includes at least one opening 12800.
In one embodiment, the at least one channel 12850 is in fluid
communication with at least one fluidics device (FIGS.
128C-128D).
In one embodiment, the array device includes at least one channel
12890. In one embodiment, the at least one channel 12890 includes
at least one cross-coupling flow channel 12890. In one embodiment,
the array device includes at least one compartment 12870. In one
embodiment, the at least one compartment 12870 is in fluid
communication with the at least one channel 12890. In one
embodiment, the array device includes at least one agent. In one
embodiment, the agent is included in the at least one compartment
12870. In one embodiment, the at least one compartment is
configured to hold at least one agent, or at least one material
extracted from at least one substrate 12895.
In one embodiment, at least one frozen piercing implement of the
plurality of frozen piercing implements includes at least one inlet
port 12800A or 12800B. In one embodiment, the at least one inlet
port 12800A or 12800B is in fluid communication with at least one
channel 12890 of at least one frozen piercing implement. In one
embodiment, the at least one inlet port 12800A or 12800B is in
fluid communication with at least one channel 12890 of the array
device. In one embodiment, at least one frozen piercing implement
of the plurality of frozen piercing implements includes a plurality
of inlet ports. In one embodiment, at least one frozen piercing
implement of the plurality of frozen piercing implements includes
at least one outlet port 12800B or 12800A. In one embodiment, the
at least one outlet port 12800B or 12800A is in fluid communication
with at least one channel 12890 of at least one frozen piercing
implement. In one embodiment, the at least one outlet port 12800B
or 12800A is in fluid communication with at least one channel 12890
of the array device. In one embodiment, at least one frozen
piercing implement of the plurality of frozen piercing implements
includes a plurality of outlet ports 12800B or 12800A.
In one embodiment, the array device further comprises at least one
of a nanoparticle, microparticle, sensor, valve, gate, channel,
transducer, actuator, detector, heater, circuit, or detection
material. The location of these features may vary according to the
device (e.g., the distal end 12810, the proximal end 12820, any
location along the shaft or channel of the implement 12800, 12830).
See, for particular non-limiting examples, FIGS. 128, and 129.
As illustrated in FIG. 129, in one embodiment, the frozen piercing
implement device includes at least one actuator structure 12910,
optionally integral with the at least one support structure 12925
of the frozen piercing implement(s). In one embodiment, a fluidic
device comprises at least one frozen piercing implement, and at
least one actuator 12910 configured to actuate the at least one
frozen piercing implement 12800.
In one embodiment, the at least one actuator 12910 includes at
least one of a piezoelectric actuator, electrostatic actuator,
thermal actuator, shape-memory alloy actuator, bioactuator, or
magnetic actuator. In one embodiment, the actuator includes a
microactuator or a nanoactuator. In one embodiment, at least one
feature 12940 or 12930 (e.g., channel, pump, sensor, injector,
actuator, heater, detector, controller, transducer, receiver,
cooler, transmitter, circuit, lens, tunablelens, valve, gate,
nanoparticle, microparticle, power source, or detection material,
etc.) is located in the body 12900 of the device. In one
embodiment, the valve includes at least one of a one-way valve, or
pressure settable valve.
In one embodiment, the at least compartment 12920 is configured to
hold at least one material extracted from at least one substrate
12970. In one embodiment, the fluidic device includes at least one
means for drawing up the at least one material from the at least
one substrate 12970. In one embodiment, at least one piercing
implement 12800 is in fluid communication with at least one
compartment 12920. In one embodiment, the sensor is configured to
respond to at least one material collected in the at least one
compartment 12920. In one embodiment, the at least one compartment
12920 is configured for displacement of at least one fluid as the
at least one material is extracted from the at least one substrate
12970. In at least one embodiment, the at least one compartment
12920 is substantially rigid. See, FIG. 130 for other non-limiting
examples of compartments. In one embodiment, the at least one
compartment 12920 is substantially deformable. See FIGS. 133-134
for other non-limiting examples of compartments. In one embodiment,
the fluidic device includes at least one cantilever 12955. In one
embodiment, the at least one cantilever 12955 is integral with the
at least one actuator 12910. In one embodiment, the at least one
cantilever 12955 is supported by the body 12900, or other
structures within the body 12900 of the device.
As described herein for other embodiments of frozen piercing
implements or frozen piercing implement devices, in one embodiment,
the at least one frozen piercing implement or device includes at
least one agent. Various non-limiting examples of agents are
provided herein. In particular, in one embodiment, the agent
includes at least one of an antimicrobial, citrate, EDTA,
anticoagulant, or other agent.
As described herein for other embodiments of frozen piercing
implements or frozen piercing implement devices, in one embodiment,
the at least one frozen piercing implement is configured to
transform to another phase state upon the occurrence of at least
one inducible event. In one embodiment, the at least one inducible
event includes one or more of: administration of the device to at
least one substrate, contacting the at least one frozen piercing
implement with at least one substrate, increasing the temperature
of the at least one frozen piercing implement, increasing the
temperature of the at least one substrate, increasing the pressure
on the at least one frozen piercing implement, increasing the
pressure on the at least one substrate, altering a magnetic field
on the at least one frozen piercing implement, altering a magnetic
field on the at least one substrate, administering at least one
additional agent to the at least one frozen piercing implement,
administering at least one additional agent to the substrate,
administering at least one electric field to the at least one
frozen piercing implement, administering at least one electric
field to the at least one substrate, administering ultrasound to
the at least one frozen piercing implement, administering
ultrasound to the at least one substrate.
As illustrated in FIG. 129, in one embodiment, the fluidic device
including at least one frozen piercing implement 12800, includes at
least one actuator 12910. In one embodiment, at least one
controller 12960 is configured to control the at least one actuator
12910. The controller 12960 may include, for example, a mechanical
or electrical controller. In one embodiment, the controller 12960
includes a wireless controller. In one embodiment, the device
includes at least one sensor 12950 configured to sense at least one
material extracted from the at least one substrate 12970 (e.g., the
material passes through the at least one piercing implement 12800
or is extracted by force from the at least one piercing implement
changing phase and retreating). In one embodiment, the at least one
frozen piercing implement 12800 is integral with the at least one
actuator 12910. In one embodiment, the at least one sensor is
configured to detect at least one material from the at least one
substrate 12970. Several non-limiting examples of materials capable
of being sensed are disclosed herein.
In various embodiments disclosed herein, the support structure
(e.g., 12880, 12925, 13030, etc.) includes at least one frozen
composition. In one embodiment, the support structure (12900)
includes at least one of a metal, ceramic, polymer, organic or
inorganic compound, semiconductor, other material, or composite
thereof.
In one embodiment, the at least one compartment 12920 expands as at
least one material is extracted. See FIG. 134 for other
non-limiting examples of compartments. In one embodiment, the at
least one compartment 12920 is substantially fabricated from one or
more of a polymer, metal, ceramic, semiconductor, frozen
composition, other material, or composite thereof.
In one embodiment, the at least one actuator 12910 includes at
least one of a piezoelectric actuator, electrostatic actuator,
thermal actuator, shape-memory alloy actuator, bioactuator, or
magnetic actuator. In one embodiment, the at least one frozen
piercing implement is integral with one or more of the at least one
of a channel, pump, sensor, injector, actuator, heater, detector,
controller, transducer, receiver, transmitter, circuit, lens,
cooler, tunablelens, valve, gate, channel, nanoparticle,
microparticle, power source, or detection material. See, for
example, FIGS. 127-131 for various non-limiting examples of
particular embodiments.
As illustrated in FIG. 130, in one embodiment, a frozen piercing
implement device includes at least one injection or fluidic device
13000. In one embodiment, the injection device 13000 includes at
least one auto-injection device. In one embodiment, a plurality of
piercing implements 13040, including at least one frozen piercing
implement, is employed in the injection device. In one embodiment,
a single frozen piercing implement is employed (not shown). In one
embodiment, the plurality of piercing implements 13040 are
positioned on at least one support structure 13030. In one
embodiment, the piercing implement(s) 13040 are in fluid
communication with at least one compartment 13010 configured to
hold at least one agent for administration to at least one
substrate, or at least one material extracted from at least one
substrate. In one embodiment, the piercing implement(s) 13040 can
be contracted (FIG. 130A) or extended (FIG. 130B). In one
embodiment, a mechanical controller (e.g., plunger) 13020 is
configured to control at least one of the position of the piercing
implement(s) 13040, or the level of contents of the at least one
compartment 13010.
In one embodiment, at least one first implement of the plurality of
implements 13040 is configured to deliver at least one agent, and
at least one second implement of the plurliaty of implements 13040
is configured to sense or extract at least one material from the at
least one substrate 13050. In one embodiment, the at least one
first implement is configured to deliver an agent that is different
than the at least one second implement.
In one embodiment, the fluidic device includes at least one of a
channel, pump, sensor, injector, actuatory, heater, detector,
controller, transducer, receiver, cooler, transmitter, circuit,
lens, tunablelens, valve, gate, nanoparticle, microparticle, power
source, or detection material (e.g., in the compartment, in the
support structure, in at least one frozen piercing implement,
etc.). The location of these various features can vary, depending
on the particular embodiment. For example, such features may be
found in the at least one compartment 13010, in or near the
mechanical controller 13020, near the proximal or distal end of the
at least one compartment 13010, in or near the at least one support
structure 13030, or in or near the at least one frozen piercing
implement 13040. See FIG. 129 for other non-limiting examples of
particular embodiments.
As illustrated in FIG. 131, a frozen piercing implement device
including a plurality of piercing implements, including at least
one frozen piercing implement 12600, includes at least one topside
of a support structure 13180, and at least one underside of the at
least one support structure 13190. In one embodiment, the frozen
piercing implement device can be fabricated into various shapes
(13100, 13120, 13140, 13160) or configurations (13110, 13130,
13150, 13170).
As illustrated in FIG. 132, a frozen piercing implement device
13205 is included in at least one system 13200 for administration
to at least one substrate 13250, or extraction of at least one
material from at least one substrate 13250. In one embodiment, the
device includes at least two electrode assemblies (13210, 13212)
and an integrated power source 13220. In one embodiment, the device
includes at least one frozen piercing implement 13230, and at least
one support structure 13240.
As illustrated in FIGS. 133-134, in one embodiment, the array
device includes a plurality of compartments 13370 in fluid
communication with at least one frozen piercing implement 13360 of
the plurality of frozen piercing implements 13380. In one
embodiment, the plurality of compartments 13370 includes at least
one first compartment (e.g., 13370A) configured to hold at least
one different substance from at least one second compartment (e.g.,
13370B or 13370C).
In one embodiment, the plurality of compartments 13370 includes at
least one first compartment (e.g., 13370A) configured to hold at
least one first agent, wherein the at least one first agent is
different from at least one other agent located in at least one
second compartment (e.g., 13370B or 13370C). In one embodiment, the
plurality of compartments 13370 includes at least one first
compartment configured to hold at least one first agent, and at
least one second compartment configured to hold a pharmaceutically
acceptable carrier or excipient.
In one embodiment, two or more compartments (e.g., 13370A, 13370B,
or 13370C) are configured to interact with at least one means for
intermixing the contents of the two or more compartments prior to
or during administration of the array device to at least one
substrate. In one embodiment, the at least one means for
intermixing includes mechanical disruption of at least one
compartment, altering porosity of at least one compartment,
electrochemical degradation of at least one compartment, valve
opening of at least one compartment, chemical degradation of at
least one compartment, or altering magnetic field of at least one
compartment. In one embodiment, the contents of the two or more
compartments are intermixed during administration by way of contact
of the one or more piercing implements 13380 with the at least one
substrate.
In one embodiment, the array device is in electronic communication
with at least one computing device.
In one embodiment, a composition comprises a plurality of piercing
implement array devices joined together, the piercing implement
array devices including at least one frozen piercing implement.
See, for example, FIGS. 131-132 for various non-limiting examples
of arrays that can be joined together in particular
embodiments.
As illustrated in FIG. 133, in one embodiment, the frozen piercing
implement device 13300, includes at least one frozen piercing
implement 13360. In one embodiment, the at least one frozen
piercing implement 13360 includes at least one channel 13310. In
one embodiment, the at least one channel 13310 is in fluid
communication with at least one compartment 13320, or plurality of
compartments 13370. In one embodiment, the at least one compartment
is configured to hold at least one agent to be administered to the
at least one substrate, or at least one material extracted from the
at least one substrate. In one embodiment, the plurality of
compartments can include multiple compartments for administration
or extraction. In one embodiment, the same compartment can be
utilized for both administration of at least one agent, and for
collection of extracted material from the at least one substrate.
In one embodiment, the at least one frozen piercing implement 13360
is positioned on at least one support structure 13330. In one
embodiment, the at least one support structure includes at least
one frozen fluid or frozen composition. In one embodiment, the at
least one compartment 13320 is configured to at least partially
deflate (thereby expelling any contents) or at least partially
inflate (thereby extracting or collecting at least one material
from at least one substrate) by way of a separate component 13340,
including an expandable component. In one embodiment, the frozen
piercing implement device includes at least one backing member,
such as a rim or shell 13350 of the support structure configured to
secure the at least one component 13340 or at least one compartment
13320. In one embodiment, the at least one compartment 13320 is
configured to at least partially deflate or inflate by way of
direct pressure on the compartment.
In one embodiment, a composition comprises a support means for an
array device, wherein the array device includes one or more frozen
piercing implements. See, for example, FIGS. 132-134 for various
non-limiting examples of support means for various array device
embodiments (e.g., 13330). In one embodiment, the support means
13330 is seperable from the one or more frozen piercing implements.
In one embodiment, at least part of the support means 13330 is at
least partially frozen. In one embodiment, the at least partially
frozen support means 13330 and the one or more frozen piercing
implements include at least one frozen constituent in common. In
one embodiment, the one or more frozen piercing implements have at
least one major dimension of approximately one centimeter or less,
approximately one millimeter or less, approximately one micrometer
or less, approximately one nanometer, or any value
therebetween.
In one embodiment, a method of administering at least one array
device to at least one substrate comprises contacting at least one
array device to at least one substrate, wherein the array device
includes at least one frozen piercing implement.
In one embodiment, a method of vaccinating a subject comprises
administering to a subject at least one frozen piercing implement
array device; wherein the at least one frozen piercing implement
array device includes at least one frozen piercing implement
including at least one vaccine.
As illustrated in FIG. 140, in one embodiment, the frozen piercing
implement device (FIGS. 140A-C), includes at least one frozen
piercing implement 14090. In one embodiment, the device includes at
least one valve 14070. In one embodiment, the valve maintains a
sealed compartment 14060. In one embodiment, the valve maintains
air pressure equilibrium between the at least one compartment 14060
and the surrounding area during actuation of the bridge 14000.
In one embodiment, the device includes at least one compartment
14060 configured to hold at least one agent to be administered to
at least one substrate 14080, or configured to hold at least one
material extracted or collected from at least one substrate 14080.
In one embodiment, the device includes at least one actuator bridge
14000 supported by at least one support structure 14010. In one
embodiment, the device includes at least one sensor 14020 located
in the at least one compartment 14060, or sidewall 14030. In one
embodiment, the device includes at least one fastening or adhesive
mechanism 14040 for adhering the device to the at least one
substrate 14080. In one embodiment, the actuator bridge 14000 is
configured to cause the at least one frozen piercing implement
14090 to contact the at least one substrate 14080 when at least one
vertical force 14050 is placed on the bridge of the actuator
14000.
In one embodiment, the actuator is driven by at least one of
mechanical, magnetic, electric, or electromagnetic force. See, for
example, Zhao, et al., Abstract, Information Acquisition, 2005 IEEE
Int'l Conf, Jun. 27-Jul. 3, 2005, which is incorporated herein by
reference.
In on embodiment, the amount of force needed to pierce the at least
one substrate is approximately 1 mN, approximately 10 mN,
approximately 20 mN, approximately 30 mN, approximately 40 mN,
approximately 50 mN, approximately 60 mN, approximately 70 mN,
approximately 80 mN, approximately 90 mN, approximately 100 mN,
approximately 150 mN, approximately 200 mN, approximately 250 mN,
approximately 300 mN, approximately 350 mN, approximately 400 mN,
approximately 450 mN, approximately 500 mN, approximately 550 mN,
approximately 600 mN, approximately 650 mN, approximately 700 mN,
approximately 750 mN, approxiatmely 800 mN, approximately 850 mN,
approximately 900 mN, approximately 1 N, approximately 2 N,
approximately 3 N, approximately 4 N, approximately 5 N, or any
value less than or therebetween. In one embodiment, the amount of
force needed to pierce the at least one substrate includes at least
one predetermined value. In one embodiment, the amount of force
needed to pierce the at least one substrate is calculated based on
at least one characteristic or property of the substrate. In one
embodiment, the amount of force needed to pierce the at least one
substrate depends on at least one characteristic or property of the
frozen piercing implement, or frozen piercing implement device.
Examples of such properties are disclosed herein.
For example, the vertical force F, which is required to penetrate
the substrate, can be calculated by multiplying the lateral force
F.sub.1 on the bridge upon deflection, with the sine of the
deflection angle a relative to resting. In one embodiment, by
increasing the horizontal width w increases the actuation force at
the tip of the cantilever bridge. Likewise, in one embodiment, an
electrical voltage can be applied to actuate the
cantilever-tip.
In one embodiment, the frozen piercing implement device includes at
least one sensor. In one non-limiting example, the sensor includes
an electrochemical transducer in which current is converted from
chemical to electrical energy through oxidation or reduction at the
electrode surface. See, for example, U.S. Patent Application
Publication No. 20050228313, which is incorporated herein by
reference. In one embodiment, the at least one sensor includes at
least one sensor to monitor at least one material in the at least
one substrate (e.g., glucose, insulin, etc.). Some non-limiting
examples of materials that can be detected or analyzed are
disclosed herein.
In one embodiment, the transducer includes a small metal electrode
that is insulated except at a particular location where the
chemical reaction occurs. At the reaction location, several
electrochemical analytical and synthetic systems are implemented.
The type of electrode sensor utilized with the device can be varied
according to the electrical parameter being measured. For example,
in the case of glucose measurement, potentiometric and emperometric
sensors can be utilized. Id.
The output signal from the at least one sensor can be displayed,
for example, on an active or passive display. In one embodiment,
the frozen piercing implement device includes at least one power
source for operation of, for example, the actuator, sensor,
corresponding transceiver or electronics. As described herein, in
one embodiment, the power source includes, for example, a battery,
fuel cell, capacitor, or DC power supply.
As illustrated in FIGS. 135-139, a computer-implemented method
13500, comprises: 13510 receiving one or more signals that include
information related to accepting input associated with at least one
parameter for making or administering at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate; 13520 wherein the at
least one frozen particle composition or frozen piercing implement
includes at least one agent; 13530 receiving one or more signals
that include information related to evaluating the at least one
substrate for one or more indicators of administration of the at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device; 13540 processing the
information related to the input associated with at least one
parameter for making or administering the at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate and the information
related to the evaluating the at least one substrate; and 13550
generating an output to a user readable display. In one embodiment
13560, evaluating at least one substrate for one or more indicators
includes evaluating at least one of an assay, image, or gross
assessment of the at least one substrate prior to, during, or
subsequent to at least one administration of at least one frozen
particle composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 13570, the assay includes at
least one technique that includes spectroscopy, microscopy,
electrochemical detection, polynucleotide detection, histological
examination, biopsy analysis, fluorescence resonance energy
transfer, electron transfer, enzyme assay, electrical conductivity,
isoelectric focusing, chromatography, immunoprecipitation,
immunoseparation, aptamer binding, filtration, electrophoresis,
immunoassay, or radioactive assay.
In one embodiment 13610, the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 13620 receiving one or more
signals includes receiving one or more signals associated with
selection of at least one parameter for making or administering the
at least one frozen particle composition, frozen piercing
implement, or frozen piercing implement device.
In one embodiment 13630, wherein the at least one parameter for
making the at least one frozen piercing implement device includes
one or more of: constitution of the at least one frozen piercing
implement of the frozen piercing implement device, constitution of
the at least one frozen piercing implement device, formulation of
the at least one frozen piercing implement of the frozen piercing
implement device, formulation of the at least one frozen piercing
implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, physical or chemical integrity of
the at least one frozen piercing implement device, or presence or
absence of at least one microparticle, nanoparticle, lens, tunable
lens, sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, energy source, injector,
controller, receiver, transmitter, or circuit, in the at least one
frozen piercing implement or frozen piercing implement device.
In one embodiment 13710, at least one parameter for administering
the at least one frozen particle composition or frozen piercing
implement includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
In one embodiment 13720, the input associated with at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement includes one or more property
including: constitution of the at least one frozen particle
composition or frozen piercing implement, configuration of the at
least one frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement.
In one embodiment 13730, the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent.
In one embodiment 13810, the input associated with at least one
parameter for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate
includes one or more of: substrate type; substrate function;
substrate size; substrate constitution; substrate architecture;
substrate durability; substrate temperature; temperature of
administration conditions; depth of administration of the at least
one frozen particle composition or frozen piercing implement;
substrate source; one or more temporal coordinates; one or more
spatial coordinates; presence or absence of at least one agent;
presence or absence of at least one microparticle, nanoparticle,
lens, tunablelens, sensor, transducer, actuator, detector, heater,
valve, gate, channel, detection material, pump, power source,
injector, controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen particle composition or
frozen piercing implement; force of administration of the at least
one frozen particle composition or frozen piercing implement;
velocity of administration of the at least one frozen particle
composition or frozen piercing implement; quantity of frozen
particle compositions or frozen piercing implements administered;
rate of administration of more than one frozen particle
compositions or frozen piercing implements; method of
administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
In one embodiment 13820, the at least one substrate includes one or
more of a cell, tissue, organ, structure, device, or food product.
In one embodiment 13830, the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device includes one or more of hydrogen oxide, nitrogen,
oxygen, air, helium, neon, argon, xenon, chlorine, bromine, carbon
dioxide, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, tetrahydrofuran, acetonitrile, acetic acid,
n-butanol, isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 13910, the output includes one or more
instructions for making the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 13920, the output includes at
least one graphical description of the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 13930, the user includes at
least one entity. In one embodiment 13940, the entity includes at
least one person, or computer. In one embodiment 13950, the user
readable display includes a human readable display. In one
embodiment 13960, the user readable display includes one or more
active displays. In one embodiment 13970, the user readable display
includes one or more passive displays. In one embodiment 13980, the
user readable display includes one or more of a numeric format,
graphical format, or audio format. In one embodiment 13990, the
user readable display includes one or more of a display of one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
property of the at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device. In one
embodiment 13995, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition, frozen piercing implement,
or frozen piercing implement device.
As illustrated in FIGS. 141-147, a computer-implemented method
14100 comprises 14110 accepting a first input associated with at
least one parameter for making at least one frozen particle
composition or frozen piercing implement; 14120 accepting a second
input associated with at least one parameter for administering the
at least one frozen particle composition or frozen piercing
implement to at least one substrate; and 14160 processing results
of the first input and the second input. In one embodiment, 14130
wherein the at least one frozen particle composition or frozen
piercing implement includes at least one agent. In one embodiment,
14140 wherein the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment, 14150 the at least one substrate includes one or more
of a cell, tissue, organ, structure, or device.
In one embodiment, 14170 processing results of the first input and
the second input includes electronically processing results of the
first input and the second input. In one embodiment, 14180
electronically processing results of the first input and the second
input by utilizing one or more of Gaussian smoothing, scaling,
homomorphic filtering, parametric estimation techniques, Boolean
operations, Monte Carlo simulations, wavelet based techniques,
mirroring, smoothing, gradient weighted partial differential
equation smoothing, NURBS, polygonal modeling, splines and patches
modeling, algorithmic execution, logical decision-making, result
prediction, Finite Element Analysis, or modification of a CAD
design.
In one embodiment, 14210 the first input includes one or more
values related to the at least one parameter for making the at
least one frozen particle composition or frozen piercing implement.
In one embodiment, 14220 the first input includes one or more
values derived from at least one image of at least one frozen
particle composition or frozen piercing implement. In one
embodiment, 14230 the at least one image includes one or more
images acquired by at least one of laser, holography, x-ray,
crystallography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment, 14250 the at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement includes one or more property
including: constitution of the at least one frozen particle
composition or frozen piercing implement, configuration of the at
least one frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, or physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14310 the at least one
parameter for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate
includes one or more of: substrate type; substrate function;
substrate size; substrate constitution; substrate architecture;
substrate durability; substrate temperature; temperature of
administration conditions; depth of administration of the at least
one frozen particle composition or frozen piercing implement;
substrate source; one or more temporal coordinates; one or more
spatial coordinates; presence or absence of at least one agent;
presence or absence of one or more sensors, valves, gates,
channels, transducers, circuits, nanoparticles, microactuators,
microdetectors, microheaters, or detection materials; angle of
administration of the at least one frozen particle composition or
frozen piercing implement; velocity of administration of the at
least one frozen particle composition or frozen piercing implement;
quantity of frozen particle compositions or frozen piercing
implements administered; rate of administration of more than one
frozen particle compositions or frozen piercing implements; method
of administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
In one embodiment, 14330 the at least one biological tissue is
located in at least one of in situ, in vitro, in vivo, in utero, in
planta, in silico, or ex vivo. In one embodiment, 14340 the at
least one substrate is at least partially located in at least one
subject. In one embodiment, 14350 the method further comprises
accepting a third input associated with at least one feature of the
at least one subject. In one embodiment, 14360 the at least one
feature of the at least one subject includes one or more of age,
gender, genotype, phenotype, proteomic profile, lipidomic profile,
glycomic profile, system biology profile, circulatory condition,
respiratory condition, blood condition, lymph condition, anatomic
landscape, body contour, or health condition.
In one embodiment, 14410 the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement includes at least one parameter relating to
administering at least one of a therapeutic agent, adhesive agent,
biological remodeling agent, reinforcement agent, abrasive, or
explosive material by way of the at least one frozen particle
composition or frozen piercing implement.
In one embodiment, 14420 the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement includes at least one parameter relating to at
least partially ablating or at least partially abrading one or more
surfaces of the at least one substrate with the at least one frozen
particle composition or frozen piercing implement. In one
embodiment, 14430 the processing results of the first input and the
second input includes determining at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement from one or more values derived from at least
one image of the at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14440 the second input
includes one or more values related to the at least one parameter
for administering at least one frozen particle composition or
frozen piercing implement. In one embodiment, 14450 the one or more
values related to the at least one parameter for administering at
least one frozen particle composition or frozen piercing implement
includes one or more predictive values.
In one embodiment, 14460 the processing results includes comparing
at least one value related to the first input associated with the
at least one parameter for making the at least one frozen particle
composition or frozen piercing implement with at least one value
related to at least one property of the frozen particle composition
or frozen piercing implement. In one embodiment, 14470 the
processing results includes determining one or more differences in
at least one value related to the first input and at least one
value related to at least one image of the at least one frozen
particle composition or frozen piercing implement.
In one embodiment, 14510 the processing results includes
determining one or more differences in at least one value related
to the second input associated with the at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14520 the processing results
includes generating one or more protocols for administering the at
least one frozen particle composition or frozen piercing implement.
In one embodiment, 14530 the administering at least one frozen
particle composition or frozen piercing implement to at least one
substrate includes delivering at least one agent to at least one
substrate.
In one embodiment, 14550, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment, 14560
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment, 14570 the user includes at least one entity. In
one embodiment 14575, the entity includes at least one person, or
computer. In one embodiment 14580, the user readable display
includes a human readable display. In one embodiment 14590, the
user readable display includes one or more active displays. In one
embodiment 14595, the user readable display includes one or more
passive displays.
In one embodiment, 14598 the user readable display includes one or
more of a numeric format, graphical format, or audio format.
In one embodiment, 14610 the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the first input and at least one
value related to at least one property of the at least one frozen
particle composition or frozen piercing implement. In one
embodiment, 14615 the user readable display includes one or more
displays of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 14618, the method further comprises transmitting
one or more signals that include information related to the
processing results of the first input and the second input. In one
embodiment, 14620 the transmitting one or more signals includes
transmitting one or more signals associated with selection of at
least one parameter for making at least one frozen particle
composition or frozen piercing implement. In one embodiment, 14630
the transmitting one or more signals includes transmitting one or
more signals associated with selection of at least one parameter
for making the at least one frozen particle composition or frozen
piercing implement. In one embodiment, 14640 the transmitting one
or more signals includes transmitting one or more signals
associated with comparing the information related to the processing
results of the first input and the second input. In one embodiment,
14650 the at least one frozen particle composition or frozen
piercing implement includes one or more of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 14710, the method further comprises making at
least one frozen particle composition or frozen piercing implement.
In one embodiment, the method 14720 further comprises administering
at least one frozen particle composition or frozen piercing
implement to at least one substrate. In one embodiment, 14730 the
method further comprises evaluating the at least one substrate for
one or more indicators related to at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement. In one embodiment, 14740 wherein the
evaluating at least one substrate for one or more indicators
includes evaluating at least one of an assay, image, or gross
assessment of the at least one substrate prior to, during, or
subsequent to at least one administration of the at least one
frozen particle composition or frozen piercing implement. In one
embodiment, 14750 the assay includes at least one technique
including spectroscopy, microscopy, electrochemical detection,
polynucleotide detection, histological examination, biopsy
analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay.
In one embodiment 14755 the at least one image includes one or more
images acquired by at least one of a laser, holography, x-ray
crystallography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
In one embodiment, 14760 the method further comprises transmitting
one or more signals that include information relating to the
accepting a first input or a second input and information related
to the evaluating the at least one substrate. In one embodiment,
14770 the transmitting one or more signals includes transmitting
one or more signals associated with selection of at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement. In one embodiment, 14780 the
transmitting one or more signals includes transmitting one or more
signals associated with selection of at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement.
As illustrated in FIGS. 148-150, in one embodiment, a
computer-implemented method 14800, comprises 14810 receiving one or
more signals that include information related to accepting input
associated with at least one parameter for making or administering
at least one frozen particle composition or frozen piercing
implement to at least one substrate; 14820 receiving one or more
signals that include information related to evaluating the at least
one substrate for one or more indicators of administration of the
at least one frozen particle composition, or frozen piercing
implement; and 14830 processing the information related to the
input associated with at least one parameter for making or
administering the at least one frozen particle composition or
frozen piercing implement to at least one substrate and the
information related to the evaluating the at least one
substrate.
In one embodiment, 14840 the at least one frozen particle
composition or frozen piercing implement includes at least one
agent. In one embodiment, 14850 wherein the evaluating at least one
substrate for one or more indicators includes evaluating at least
one of an assay, image, or gross assessment of the at least one
substrate prior to, during, or subsequent to at least one
administration of at least one frozen particle composition or
frozen piercing implement. In one embodiment, 14860 wherein the
assay includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay. In one
embodiment, 14870 wherein the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
In one embodiment, 14910 wherein the input associated with at least
one parameter for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate
includes one or more of: substrate type; substrate function;
substrate size; substrate constitution; substrate architecture;
substrate durability; substrate temperature; temperature of
administration conditions; depth of administration of the at least
one frozen particle composition or frozen piercing implement;
substrate source; one or more temporal coordinates; one or more
spatial coordinates; presence or absence of at least one agent;
presence or absence of at least one microparticle, nanoparticle,
lens, tunable lens, sensor, regulator, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
energy source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
particle composition or frozen piercing implement; velocity of
administration of the at least one frozen particle composition or
frozen piercing implement; quantity of frozen particle compositions
or frozen piercing implements administered; rate of administration
of more than one frozen particle compositions or frozen piercing
implements; method of administration of at least one frozen
particle composition or frozen piercing implement; timing of
administration of at least one frozen particle composition or
frozen piercing implement; or rate of delivery of at least one
agent.
In one embodiment, 14920 wherein the input associated with at least
one parameter for making the at least one frozen particle
composition or frozen piercing implement includes one or more
property including: constitution of the at least one frozen
particle composition or frozen piercing implement, formulation of
the at least one frozen particle composition or frozen piercing
implement, size of the at least one frozen particle composition or
frozen piercing implement, density of the at least one frozen
particle composition or frozen piercing implement, shape of the at
least one frozen particle composition or frozen piercing implement,
physical structure of the at least one frozen particle composition
or frozen piercing implement, or physical or chemical integrity of
the at least one frozen particle composition or frozen piercing
implement.
In one embodiment, 15010 the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment, 15020 the receiving one or more signals includes
receiving one or more signals associated with selection of at least
one parameter for making or administering the at least one frozen
particle composition or frozen piercing implement. In one
embodiment, 15030 wherein the at least one substrate includes one
or more of a cell, tissue, organ, structure, device, or food
product. In one embodiment, 15040 wherein the at least one frozen
particle composition or frozen piercing implement includes one or
more of hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon,
xenon, chlorine, bromine, carbon dioxide, acetone, ethyl acetate,
dimethyl sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 15050, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 15055
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 15060, the user includes at least one entity. In
one embodiment 15065, the entity includes at least one person, or
computer. In one embodiment 15070, the user readable display
includes a human readable display. In one embodiment 15080, the
user readable display includes one or more active displays. In one
embodiment 15090, the user readable display includes one or more
passive displays. In one embodiment 15095, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 15096 the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to th first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 15097, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 151-157, in one embodiment, a
computer-implemented method 15100 comprises 15110 accepting a first
input associated with at least one parameter for making at least
one frozen piercing implement device; 15120 accepting a second
input associated with at least one parameter for administering the
at least one frozen piercing implement device to at least one
substrate; 15180 processing results of the first input and the
second input; and 15198 generating an output to a user readable
display. In one embodiment, 15125 the at least one substrate
includes one or more of a cell, tissue, organ, structure, device or
food product. In one embodiment, 15130 the at least one frozen
piercing implement device includes at least one of a frozen
piercing implement array device, frozen piercing implement fluidic
device, or frozen piercing implement injection device. In one
embodiment, 15140 the frozen piercing implement injection device
includes a frozen piercing implement auto-injection device. In one
embodiment, 15150 wherein the at least one frozen piercing
implement device includes at least one agent. In one embodiment,
15160 wherein the at least one agent includes one or more of a
therapeutic agent, adhesive agent, abrasive, reinforcement agent,
explosive material, or biological remodeling agent. In one
embodiment, 15170 wherein the at least one agent is located in at
least one frozen piercing implement of the device. In one
embodiment, 15190 processing results of the first input and the
second input includes electronically processing results of the
first input and the second input. In one embodiment, 15195
electronically processing results of the first input and the second
input by utilizing one or more of Gaussian smoothing, scaling,
homomorphic filtering, parametric estimation techniques, Boolean
operations, Monte Carlo simulations, wavelet based techniques,
mirroring, smoothing, gradient weighted partial differential
equation smoothing, NURBS, polygonal modeling, splines and patches
modeling, algorithmic execution, logical decision-making, result
prediction, Finite Element Analysis, or modification of a CAD
design.
In one embodiment, 15210 the first input includes one or more
values related to the at least one parameter for making the at
least one frozen piercing implement device. In one embodiment,
15220 wherein the at least one parameter for making the at least
one frozen piercing implement device includes one or more of:
constitution of the at least one frozen piercing implement of the
frozen piercing implement device, constitution of the at least one
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunable lens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, energy source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device. In one
embodiment, 15230 the at least one parameter for administering at
least one frozen piercing implement device to at least one
substrate includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunable lens, sensor, regulator, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, energy source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
In one embodiment, 15310 the one or more values related to the at
least one parameter for administering at least one frozen piercing
implement device includes one or more predictive values. In one
embodiment, 15320 the at least one parameter for administering at
least one frozen piercing implement device includes at least one
parameter relating to at least partially ablating or at least
partially abrading one or more surfaces of the at least one
substrate with the at least one frozen piercing implement device.
In one embodiment, 15330 the first input includes one or more
values derived from at least one property of at least one frozen
piercing implement device. In one embodiment, 15340 the at least
one substrate is located in at least one of in situ, in vitro, in
vivo, in utero, in planta, in silico, or ex vivo. In one
embodiment, 15350 the at least one substrate is at least partially
located in at least one subject. In one embodiment, the method
15360 further comprises accepting a third input associated with at
least one feature of the at least one subject. In one embodiment,
the at least one feature of the at least one subject includes one
or more of age, gender, genotype, phenotype, proteomic profile,
anatomic landscape, body contour, or health condition. In one
embodiment 15370, the at least one feature of the at least one
subject includes one or more of age, gender, genotype, phenotype,
proteomic profile, lipidomic profile, glycomic profile, system
biology profile, lymph condition, circulatory condition,
respiratory condition, blood condition, anatomic landscape, body
contour, or health condition. In one embodiment, 15380 the output
includes one or more instructions for making the at least one
frozen particle composition or frozen piercing implement. In one
embodiment, 15390 the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement.
In one embodiment 15407, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the first input and at least one
value related to at least one property of the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 15408, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment, 15410 the processing results of the first input
and the second input includes determining at least one parameter
for making at least one frozen piercing implement device from one
or more values derived from at least one characteristic of at least
one frozen piercing implement of the frozen piercing implement
device. In one embodiment, 15420 the second input includes one or
more values related to the at least one parameter for administering
at least one frozen piercing implement device to the at least one
substrate. In one embodiment, 15430 the processing results includes
comparing at least one value related to the first input associated
with the at least one parameter for making the frozen piercing
implement device with at least one value related to at least one
property of the at least one frozen piercing implement. In one
embodiment, 15440 the processing results includes determining one
or more differences in at least one value related to the first
input and at least one value related to at least one property of
the at least one frozen piercing implement device. In one
embodiment, 15450 the processing results includes determining one
or more differences in at least one value related to the second
input associated with the one or more parameters of administering
at least one frozen piercing implement device to the at least one
substrate. In one embodiment, 15460 the processing results includes
generating one or more protocols for administering the at least one
frozen piercing implement device. In one embodiment, 15510 the
administering at least one frozen piercing implement device
includes delivering at least one agent to the at least one
substrate by way of the at least one frozen piercing implement
device.
In one embodiment 15518, the user includes at least one entity. In
one embodiment 15520, the entity includes at least one person, or
computer. In one embodiment 15530, the user readable display
includes a human readable display. In one embodiment 15540, the
user readable display includes one or more active displays. In one
embodiment 15550, the user readable display includes one or more
passive displays.
In one embodiment 15560, the user readable display includes one or
more of a numeric format, graphical format, or audio format. In one
embodiment 15570 the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to th first input and at least one value related
to at least one property of the at least one frozen particle
composition or frozen piercing implement. In one embodiment 15580,
the user readable display includes one or more of a display of one
or more differences in the comparison of at least one value related
to the second input and at least one value related to at least one
parameter for administration of the at least one frozen particle
composition or frozen piercing implement.
In one embodiment, the method 15610 further comprises transmitting
one or more signals that include information related to the
processing results of the first input and the second input. In one
embodiment, 15620 the transmitting one or more signals includes
transmitting one or more signals associated with selection of at
least one parameter for making the at least one frozen piercing
implement device. In one embodiment, 15630 the transmitting one or
more signals includes transmitting one or more signals associated
with selection of one or more agents to be delivered by the at
least one frozen piercing implement device. In one embodiment,
15640 wherein the transmitting one or more signals includes
transmitting one or more signals associated with comparing the
information related to the processing results of the first input
and the second input. In one embodiment, 15650 wherein the at least
one frozen piercing implement device includes one or more frozen
piercing implements that include at least one of hydrogen oxide,
nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetronitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, standard saline
citrate, methane, toluene, chloroform, polyethylene glycol, acetic
acid, Ringer's solution, lactated Ringer's solution, Hartmann's
solution, acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment, the method 15710 further comprises making at
least one frozen piercing implement device. In one embodiment, the
method 15720 further comprises administering at least one frozen
piercing implement device to at least one substrate. In one
embodiment, the method 15730 further comprises evaluating the at
least one substrate for one or more indicators related to at least
one parameter for administering the at least one frozen piercing
implement device. In one embodiment, 15740 the evaluating at least
one substrate for one or more indicators includes evaluating at
least one of an assay, image, or gross assessment of the at least
one substrate prior to, during, or subsequent to at least one
administration of the at least one frozen piercing implement
device. In one embodiment, 15750 the assay includes at least one
technique including spectroscopy, microscopy, electrochemical
detection, polynucleotide detection, histological examination,
biopsy analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment,15755 wherein the at least one
image includes one or more images acquired by at least one of
laser, holography, x-ray, crystallography, optical coherence
tomography, computer-assisted tomography scan, computed tomography,
magnetic resonance imaging, positron-emission tomography scan,
ultrasound, x-ray, electrical-impedance monitoring, microscopy,
spectrometry, flow cytommetry, radioisotope imaging, thermal
imaging, infrared visualization, multiphoton calcium-imaging,
photography, or in silico generation
In one embodiment, the method 15760 further comprises transmitting
one or more signals that include information relating to the
accepting a first input or a second input and information related
to the evaluating the at least one substrate. In one embodiment,
15770 the transmitting one or more signals includes transmitting
one or more signals associated with selection of at least one
parameter for making the at least one frozen piercing implement
device. In one embodiment, 15780 wherein the transmitting one or
more signals includes transmitting one or more signals associated
with selection of at least one parameter for administering the at
least one frozen piercing implement device.
As illustrated in FIGS. 158-160 a computer-implemented method 15800
comprises 15810 receiving one or more signals that include
information related to accepting input associated with at least one
parameter for making or administering at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate; wherein the at least
one frozen particle composition, frozen piercing implement, or
frozen piercing implement device includes at least one agent; 15820
receiving one or more signals that include information related to
evaluating the at least one substrate for one or more indicators of
administration of the at least one frozen particle composition,
frozen piercing implement, frozen piercing implement device, or
agent; and 15830 processing the information related to the input
associated with at least one parameter for making or administering
the at least one frozen piercing implement device to at least one
substrate and the information related to the evaluating the at
least one substrate. In one embodiment, 15840 wherein the
evaluating at least one substrate for one or more indicators
includes evaluating at least one of an assay, image, or gross
assessment of the at least one substrate prior to, during, or
subsequent to at least one administration of at least one frozen
piercing implement device. In one embodiment, 15850 the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay. In one
embodiment, 15860 wherein the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment, 15870 wherein the receiving
one or more signals includes receiving one or more signals
associated with selection of at least one parameter for making or
administering the at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device.
In one embodiment, 15910 the at least one parameter for making the
at least one frozen piercing implement device includes one or more
of: constitution of the at least one frozen piercing implement of
the frozen piercing implement device, constitution of the at least
one frozen piercing implement device, formulation of the at least
one frozen piercing implement of the frozen piercing implement
device, formulation of the at least one frozen piercing implement
device, size of the at least one frozen piercing implement of the
frozen piercing implement device, size of the at least one frozen
piercing implement device, shape of the at least one frozen
piercing implement of the frozen piercing implement device, shape
of the at least one frozen piercing implement device, physical
structure of the at least one frozen piercing implement of the
frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, physical or chemical integrity of
the at least one frozen piercing implement device, or presence or
absence of at least one microparticle, nanoparticle, lens, tunable
lens, sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, energy source, injector,
controller, receiver, transmitter, or circuit, in the at least one
frozen piercing implement or frozen piercing implement device.
In one embodiment, 15920 wherein the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunable lens, sensor, regulator,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, energy source, injector, controller,
receiver, transmitter, or circuit; angle of administration of the
at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
In one embodiment, 16010 the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment, 16020 wherein the at least one substrate includes
one or more of a cell, tissue, organ, structure, device, or food
product.
In one embodiment, 16030 wherein the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device includes one or more of hydrogen oxide, nitrogen,
oxygen, air, helium, neon, argon, xenon, chlorine, bromine, carbon
dioxide, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl
formamide, dioxane, tetrahydrofuran, acetronitrile, acetic acid,
n-butanol, isopropanol, n-propanol, hexamethylphosphorotriamide,
perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic
acid, hydrogen fluoride, ammonia, benzene, carbon tetrachloride,
hexane, dichloromethane, methylene chloride, carboxylic acid,
saline, standard saline citrate, methane, toluene, chloroform,
polyethylene glycol, acetic acid, Ringer's solution, lactated
Ringer's solution, Hartmann's solution, acetated Ringer's solution,
phosphate buffered solution, TRIS-buffered saline solution, Hank's
balanced salt solution, Earle's balanced salt solution, standard
saline citrate, HEPES-buffered saline, dextrose, glucose, or
diethyl ether.
In one embodiment 16035, the output includes one or more
instructions for making the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 16040, the output includes at
least one graphical description of the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device.
In one embodiment 16050, the user includes at least one entity. In
one embodiment 16055, the entity includes at least one person, or
computer. In one embodiment 16060, the user readable display
includes a human readable display. In one embodiment 16065, the
user readable display includes one or more active displays. In one
embodiment 16070, the user readable display includes one or more
passive displays. In one embodiment 16075, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 16076 the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to th first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 16077, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
In one embodiment 16110, at least one parameter for making the at
least one frozen particle composition or frozen piercing implement
includes one or more of: constitution of the at least one frozen
particle composition or frozen piercing implement, formulation of
the at least one frozen particle composition or frozen piercing
implement, size of the at least one frozen particle composition or
frozen piercing implement, density of the at least one frozen
particle composition or frozen piercing implement, shape of the at
least one frozen particle composition or frozen piercing implement,
physical structure of the at least one frozen particle composition
or frozen piercing implement, physical or chemical integrity of the
at least one frozen particle composition or frozen piercing
implement, or presence or absence of a microparticle, nanoparticle,
lens, tunable lens, sensor, transducer, actuator, detector, heater,
valve, gate, channel, detection material, pump, energy source,
injector, controller, receiver, transmitter, or circuit.
In one embodiment 16120, at least one parameter for administering
the at least one frozen particle composition or frozen piercing
implement includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
As illustrated in FIG. 162, in one embodiment, a method 16200
comprises 16210 making at least one frozen particle composition,
frozen piercing implement, or frozen piercing implement device; and
16220 administering at least one frozen particle composition,
frozen piercing implement, or frozen piercing implement device to
at least one substrate. In one embodiment, the method 16200
includes a computer-implemented method.
As illustrated in FIGS. 163-166, a system 16300 comprises: 16310
means for receiving one or more signals that include information
related to accepting input associated with at least one parameter
for making or administering at least one frozen particle
composition or frozen piercing implement to at least one substrate,
the frozen particle composition or frozen piercing implement
including at least one agent; 16320 means for receiving one or more
signals that include information related to evaluating the at least
one substrate for one or more indicators of administration of the
at least one frozen particle composition, frozen piercing
implement, or agent; 16330 means for processing the information
related to the input associated with at least one parameter for
making or administering the at least one frozen particle
composition or frozen piercing implement to at least one substrate
and the information related to the evaluating the at least one
substrate; and 16340 means for generating an output to a user
readable display. In one embodiment 16350, evaluating at least one
substrate for one or more indicators includes evaluating at least
one of an assay, image, or gross assessment of the at least one
biological tissue prior to, during, or subsequent to at least one
administration of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 16360, the assay
includes at least one technique that includes spectroscopy,
microscopy, electrochemical detection, polynucleotide detection,
histological examination, biopsy analysis, fluorescence resonance
energy transfer, electron transfer, enzyme assay, electrical
conductivity, isoelectric focusing, chromatography,
immunoprecipitation, immunoseparation, aptamer binding, filtration,
electrophoresis, immunoassay, or radioactive assay.
In one embodiment 16370, the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 16410, the input associated
with at least one parameter for administering at least one frozen
particle composition or frozen piercing implement to at least one
substrate includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
particle composition or frozen piercing implement; force of
administration of the at least one frozen particle composition or
frozen piercing implement; velocity of administration of the at
least one frozen particle composition or frozen piercing implement;
quantity of frozen particle compositions or frozen piercing
implements administered; rate of administration of more than one
frozen particle compositions or frozen piercing implements; method
of administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
In one embodiment 16420, the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 16430, the means for receiving one or more signals
includes means for receiving one or more signals associated with
selection of at least one parameter for making the at least one
frozen particle composition or frozen piercing implement. In one
embodiment 16440, the at least one parameter for making the at
least one frozen particle composition or frozen piercing implement
includes one or more property including: constitution of the at
least one frozen particle composition or frozen piercing implement,
configuration of the at least one frozen particle composition or
frozen piercing implement, formulation of the at least one frozen
particle composition or frozen piercing implement, size of the at
least one frozen particle composition or frozen piercing implement,
density of the at least one frozen particle composition or frozen
piercing implement, shape of the at least one frozen particle
composition or frozen piercing implement, physical structure of the
at least one frozen particle composition or frozen piercing
implement, physical or chemical integrity of the at least one
frozen particle composition or frozen piercing implement.
In one embodiment 16510, the at least one substrate includes one or
more of a cell, tissue, organ, structure, device, or food product.
In one embodiment 16520, the at least one frozen particle
composition or frozen piercing implement includes one or more of
hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon, xenon,
chlorine, bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, methane, toluene,
chloroform, polyethylene glycol, acetic acid, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether.
In one embodiment 16530, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 16540,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 16550, the user includes at least one entity. In
one embodiment 16560, the entity includes at least one person, or
computer. In one embodiment 16570, the user readable display
includes a human readable display. In one embodiment 16580, the
user readable display includes one or more active displays. In one
embodiment 16590, the user readable display includes one or more
passive displays. In one embodiment 16595, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 16610, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 16620, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 167-174, a system 16700 comprises: 16710
means for accepting a first input associated with at least one
parameter for making at least one frozen piercing implement device;
16720 means for accepting a second input associated with at least
one parameter for administering the at least one frozen piercing
implement device to at least one substrate; 16730 means for
processing the first input and the second input; and 16740 means
for generating an output to a user readable display.
In one embodiment 16750, the at least one frozen piercing implement
device includes at least one of a frozen piercing implement array
device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 16760, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
In one embodiment 16770, the means for processing the first input
and the second input includes means for electronically processing
the first input and the second input. In one embodiment 16780, the
means for processing the first input and the second input includes
means for electronically processing the first input and the second
input by utilizing one or more of Gaussian smoothing, scaling,
homomorphic filtering, parametric estimation techniques, Boolean
operations, Monte Carlo simulations, wavelet based techniques,
mirroring, smoothing, gradient weighted partial differential
equation smoothing, NURBS, polygonal modeling, splines and patches
modeling, algorithmic execution, logical decision-making, result
prediction, Finite Element Analysis, or modification of a CAD
design.
In one embodiment 16810, the frozen piercing implement device
includes at least one agent. In one embodiment 16820, the at least
one agent is located in at least one frozen piercing implement of
the device. In one embodiment 16830, the at least one agent
includes one or more of a therapeutic agent, adhesive agent,
abrasive, reinforcement agent, explosive material, or biological
remodeling agent. In one embodiment 16840, the at least one
substrate includes one or more of a cell, tissue, organ, structure,
device, or food product. In one embodiment 16850, the first input
includes one or more values related to the at least one parameter
for making the at least one frozen piercing implement device. In
one embodiment 16860, the at least one parameter for making the at
least one frozen piercing implement device includes one or more of:
constitution of the at least one frozen piercing implement of the
frozen piercing implement device, constitution of the at least one
frozen piercing implement device, configuration of the at least one
frozen piercing implement, configuration of the at least one frozen
piercing implement or frozen piercing implement device, formulation
of the at least one frozen piercing implement of the frozen
piercing implement device, formulation of the at least one frozen
piercing implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, or physical or chemical integrity
of the at least one frozen piercing implement device.
In one embodiment 16910, the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
In one embodiment 16920, the at least one parameter for
administering at least one frozen piercing implement device
includes at least one parameter relating to at least partially
ablating or at least partially abrading one or more surfaces of the
at least one substrate with the at least one frozen piercing
implement device. In one embodiment 16930, the first input includes
one or more values derived from at least one property of at least
one frozen piercing implement device. In one embodiment 16940, the
at least one substrate is located in at least one of in situ, in
vitro, in vivo, in utero, in planta, in silico, or ex vivo. In one
embodiment 16950, the at least one substrate is at least partially
located in at least one subject.
In one embodiment 16960, the system further comprises means for
accepting a third input associated with at least one feature of the
at least one subject. In one embodiment 17010, the at least one
feature of the at least one subject includes one or more of age,
gender, genotype, phenotype, proteomic profile, lipidomic profile,
glycomic profile, system biology profile, lymph condition,
circulatory condition, respiratory condition, blood condition,
anatomic landscape, body contour, or health condition. In one
embodiment 17020, the means for processing the first input and the
second input includes means for determining at least one parameter
for administering at least one frozen piercing implement device
from one or more values derived from at least one image of at least
one frozen piercing implement of the device, or at least one image
of at least one frozen piercing implement device. In one embodiment
17030, the second input includes one or more values related to the
at least one parameter for administering at least one frozen
piercing implement device to the at least one substrate.
In one embodiment 17040, the one or more values related to the at
least one parameter for administering at least one frozen piercing
implement device includes one or more predictive values. In one
embodiment 17050, the means for processing the first input and the
second input includes means for comparing at least one value
related to the first input associated with the at least one
parameter for making the frozen piercing implement device with at
least one value related to at least one property of at least one
frozen piercing implement of the device, or at least one frozen
piercing implement device. In one embodiment 17060, the means for
processing the first input and the second input includes means for
determining one or more differences in at least one value related
to the first input and at least one value related to at least one
property of at least one frozen piercing implement device or at
least one frozen piercing implement of the device. In one
embodiment 17070, the means for processing the first input and the
second input includes means for determining one or more differences
in at least one value related to the second input associated with
the one or more parameters of administering at least one frozen
piercing implement device to the at least one substrate.
In one embodiment 17110, the means for processing the first input
and the second input includes means for generating one or more
protocols for administering the at least one frozen piercing
implement device. In one embodiment 17120, the output includes one
or more instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 17130,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 17140, the user includes at least one entity. In
one embodiment 17150, the entity includes at least one person, or
computer. In one embodiment 17160, the user readable display
includes a human readable display. In one embodiment 17170, the
user readable display includes one or more active displays. In one
embodiment 17180, the user readable display includes one or more
passive displays. In one embodiment 17185, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 17190, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement.
In one embodiment 17210, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement. In one embodiment 17220, the system further comprises
means for transmitting one or more signals that include information
related to the means for processing the first input and the second
input. In one embodiment 17230, the means for transmitting one or
more signals includes means for transmitting one or more signals
associated with selection of at least one parameter for making the
at least one frozen piercing implement device. In one embodiment
17240, the means for transmitting one or more signals includes
means for transmitting one or more signals associated with
selection of one or more agents to be delivered by the at least one
frozen piercing implement device.
In one embodiment 17250, the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 17310, the means for transmitting one or more
signals includes means for transmitting one or more signals
associated with at least one parameter for making or administering
at least one frozen piercing implement device. In one embodiment
17320, means for transmitting one or more signals includes means
for transmitting one or more signals associated with means for
comparing the information related to the means for processing the
first input and the second input. In one embodiment 17330, the at
least one frozen piercing implement device includes one or more
frozen piercing implements that include at least one of hydrogen
oxide, nitrogen, oxygen, air, helium, neon, argon, xenon, chlorine,
bromine, carbon dioxide, acetone, ethyl acetate, dimethyl
sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, methane, toluene,
chloroform, polyethylene glycol, acetic acid, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether.
In one embodiment 17340, the system further comprises means for
making at least one frozen piercing implement device. In one
embodiment 17350, the system further comprises means for
administering at least one frozen piercing implement device to at
least one substrate. In one embodiment 17360, the system further
comprises means for evaluating the at least one substrate for one
or more indicators related to at least one parameter for
administering the at least one frozen piercing implement device. In
one embodiment 17370, the means for evaluating at least one
substrate for one or more indicators includes means for evaluating
at least one of an assay, image, or gross assessment of the at
least one substrate prior to, during, or subsequent to at least one
administration of the at least one frozen particle composition or
frozen piercing implement.
In one embodiment 17410, the assay includes at least one technique
including spectroscopy, microscopy, electrochemical detection,
polynucleotide detection, histological examination, biopsy
analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 17420, the at least one image
includes one or more images acquired by at least one of laser,
holography, x-ray crystallography, optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, electrical-impedance monitoring, microscopy, spectrometry,
flow cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
In one embodiment 17430, the system further comprises means for
transmitting one or more signals that include information relating
to the accepting a first input or a second input and information
related to the evaluating the at least one substrate. In one
embodiment 17440, the means for transmitting one or more signals
includes means for transmitting one or more signals associated with
selection of at least one parameter for making the at least one
frozen particle composition or frozen piercing implement. In one
embodiment 17460, the means for transmitting one or more signals
includes means for transmitting one or more signals associated with
selection of at least one parameter for administering the at least
one frozen particle composition or frozen piercing implement.
As illustrated in FIGS. 175-181, a system 17500, comprises: 17510
means for accepting a first input associated with at least one
parameter for making at least one frozen particle composition or
frozen piercing implement; 17520 means for accepting a second input
associated with at least one parameter for administering the at
least one frozen particle composition or frozen piercing implement
to at least one substrate; 17530 means for processing the first
input and the second input; and 17540 means for generating an
output to a user readable display. In one embodiment 17550, the at
least one parameter for administering at least one frozen particle
composition or frozen piercing implement includes at least one
parameter relating to at least partially ablating or at least
partially abrading one or more surfaces of the at least one
substrate with the at least one frozen particle composition or
frozen piercing implement. In one embodiment 17560, the means for
processing the first input and the second input includes means for
electronically processing the first input and the second input. In
one embodiment 17570, the means for processing the first input and
the second input includes means for electronically processing the
first input and the second input by utilizing one or more of
Gaussian smoothing, scaling, homomorphic filtering, parametric
estimation techniques, Boolean operations, Monte Carlo simulations,
wavelet based techniques, mirroring, smoothing, gradient weighted
partial differential equation smoothing, NURBS, polygonal modeling,
splines and patches modeling, algorithmic execution, logical
decision-making, result prediction, Finite Element Analysis, or
modification of a CAD design.
In one embodiment 17580, the first input includes one or more
values related to the at least one parameter for making the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 17610, the at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement includes one or more property including: constitution of
the at least one frozen particle composition or frozen piercing
implement, configuration of the at least one frozen particle
composition or frozen piercing implement, formulation of the at
least one frozen particle composition or frozen piercing implement,
size of the at least one frozen particle composition or frozen
piercing implement, density of the at least one frozen particle
composition or frozen piercing implement, shape of the at least one
frozen particle composition or frozen piercing implement, physical
structure of the at least one frozen particle composition or frozen
piercing implement, physical or chemical integrity of the at least
one frozen particle composition or frozen piercing implement, or
presence or absence of a microparticle, nanoparticle, lens,
tunablelens, sensor, transducer, actuator, detector, heater, valve,
gate, channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit. In one embodiment
17620, the at least one parameter for administering at least one
frozen particle composition or frozen piercing implement to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of one or more sensors,
valves, gates, channels, transducers, circuits, nanoparticles,
microactuators, microdetectors, microheaters, or detection
materials; angle of administration of the at least one frozen
particle composition or frozen piercing implement; force of
administration of the at least one frozen particle composition or
frozen piercing implement velocity of administration of the at
least one frozen particle composition or frozen piercing implement;
quantity of frozen particle compositions or frozen piercing
implements administered; rate of administration of more than one
frozen particle compositions or frozen piercing implements; method
of administration of at least one frozen particle composition or
frozen piercing implement; timing of administration of at least one
frozen particle composition or frozen piercing implement; or rate
of delivery of at least one agent.
In one embodiment 17630, the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 17710, the at least one substrate includes one or
more of a cell, tissue, organ, structure, device, or food product.
In one embodiment 17720, the first input includes one or more
values derived from at least one property of the at least one
frozen particle composition or frozen piercing implement.
In one embodiment 17730, the at least one substrate is located in
at least one of in situ, in vitro, in vivo, in utero, in planta, in
silico, or ex vivo. In one embodiment 17740, the at least one
substrate is at least partially located in at least one subject. In
one embodiment 17750, the system further comprises means for
accepting a third input associated with at least one feature of the
at least one subject. In one embodiment 17760, the at least one
feature of the at least one subject includes one or more of age,
gender, genotype, phenotype, proteomic profile, lipidomic profile,
glycomic profile, system biology profile, lymph condition,
circulatory condition, respiratory condition, blood condition,
anatomic landscape, body contour, or health condition. In one
embodiment 17770, the means for processing the first input and the
second input includes means for determining at least one parameter
for administering at least one frozen particle composition or
frozen piercing implement from one or more values derived from at
least one parameter for administering the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 17780, the means for processing the first input and the
second input includes means for determining one or more differences
in at least one value related to the second input and at least one
value related to at least one parameter for administering of at
least one frozen particle composition or frozen piercing implement
to at least one substrate.
In one embodiment 17810, the second input includes one or more
values related to the at least one parameter for administering at
least one frozen particle composition or frozen piercing implement
to the at least one substrate. In one embodiment 17820, the one or
more values related to the at least one parameter for administering
at least one frozen particle composition or frozen piercing
implement includes one or more predictive values. In one embodiment
17830, the means for processing the first input and the second
input includes means for comparing at least one value related to
the first input associated with the at least one parameter for
making the at least one frozen particle composition or frozen
piercing implement with at least one value related to at least one
property of the frozen particle composition or frozen piercing
implement.
In one embodiment 17840, the means for processing the first input
and the second input includes means for determining one or more
differences in at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 19950, the means for processing the first input and
the second input includes means for generating one or more
protocols for administering the at least one frozen particle
composition or frozen piercing implement. In one embodiment 17860,
the output includes one or more instructions for making the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 17870, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 17880, the user
includes at least one entity.
In one embodiment 17910, the entity includes at least one person,
or computer. In one embodiment 17920, the user readable display
includes a human readable display. In one embodiment 17930, the
user readable display includes one or more active displays.
In one embodiment 17940, the user readable display includes one or
more passive displays. In one embodiment 17950, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 17960, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 17970, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
In one embodiment 17980, the system further comprises means for
transmitting one or more signals that include information related
to the processing of the first input and the second input. In one
embodiment 17990, the means for transmitting one or more signals
includes means for transmitting one or more signals associated with
selection of at least one parameter for making the at least one
frozen particle composition or frozen piercing implement.
In one embodiment 18010, the means for transmitting one or more
signals includes means for transmitting one or more signals
associated with comparing the information related to the processing
of the first input and the second input. In one embodiment 18020,
the means for transmitting one or more signals includes means for
transmitting one or more signals associated with comparing the
information related to the processing of the first input and the
second input. In one embodiment 18030, the at least one frozen
particle composition or frozen piercing implement includes one or
more of hydrogen oxide, nitrogen, oxygen, air, helium, neon, argon,
xenon, chlorine, bromine, carbon dioxide, acetone, ethyl acetate,
dimethyl sulfoxide, dimethyl formamide, dioxane, tetrahydrofuran,
acetonitrile, acetic acid, n-butanol, isopropanol, n-propanol,
hexamethylphosphorotriamide, perfluorohydrocarbon, methanol,
ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride,
ammonia, benzene, carbon tetrachloride, hexane, dichloromethane,
methylene chloride, carboxylic acid, saline, methane, toluene,
chloroform, polyethylene glycol, acetic acid, Ringer's solution,
lactated Ringer's solution, Hartmann's solution, acetated Ringer's
solution, phosphate buffered solution, TRIS-buffered saline
solution, Hank's balanced salt solution, Earle's balanced salt
solution, standard saline citrate, HEPES-buffered saline, dextrose,
glucose, or diethyl ether. In one embodiment 18040, the system
further comprises means for making at least one frozen particle
composition or frozen piercing implement. In one embodiment 18050,
the system further comprises means for administering at least one
frozen particle composition or frozen piercing implement to at
least one substrate. In one embodiment 18060, the system further
comprises means for evaluating the at least one substrate for one
or more indicators related to at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement. In one embodiment 18070, evaluating at
least one substrate for one or more indicators includes evaluating
at least one of an assay, image, or gross assessment of the at
least one substrate prior to, during, or subsequent to at least one
administration of the at least one frozen particle composition or
frozen piercing implement.
In one embodiment 18110, the assay includes at least one technique
including spectroscopy, microscopy, electrochemical detection,
polynucleotide detection, histological examination, biopsy
analysis, fluorescence resonance energy transfer, electron
transfer, enzyme assay, electrical conductivity, isoelectric
focusing, chromatography, immunoprecipitation, immunoseparation,
aptamer binding, filtration, electrophoresis, immunoassay, or
radioactive assay. In one embodiment 18120, the at least one image
includes one or more images acquired by at least one of laser,
holography, x-ray crystallography, optical coherence tomography,
computer-assisted tomography scan, computed tomography, magnetic
resonance imaging, positron-emission tomography scan, ultrasound,
x-ray, electrical-impedance monitoring, microscopy, spectrometry,
flow cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 18130, the system further
comprises means for transmitting one or more signals that include
information relating to the accepting a first input or a second
input and information related to the evaluating the at least one
substrate. In one embodiment 18140, the means for transmitting one
or more signals includes means for transmitting one or more signals
associated with selection of at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement. In one embodiment 18150, the means for transmitting one
or more signals includes means for transmitting one or more signals
associated with selection of at least one parameter for
administering the at least one frozen particle composition or
frozen piercing implement.
As illustrated in FIGS. 182-185, a system 18200 comprises: 18210
means for receiving one or more signals that include information
related to accepting input associated with at least one parameter
for making or administering at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate; wherein the at least
one frozen particle composition, frozen piercing implement, or
frozen piercing implement device includes at least one agent; 18220
means for receiving one or more signals that include information
related to evaluating the at least one substrate for one or more
indicators of administration of at least one frozen particle
composition, frozen piercing implement, frozen piercing implement
device, or agent; 18230 means for processing the information
related to the input associated with at least one parameter for
making or administering the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device to at least one substrate and the information
related to the evaluating the at least one substrate; and 18240
means for generating an output to a user readable display. In one
embodiment 18250, the at least one frozen piercing implement device
includes at least one of a frozen piercing implement device, frozen
piercing implement fluidic device, or frozen piercing implement
injection device. In one embodiment 18260, the frozen piercing
implement injection device includes a frozen piercing implement
auto-injection device. In one embodiment 18270, evaluating at least
one substrate for one or more indicators includes means for
evaluating at least one of an assay, image, or gross assessment of
the at least one biological tissue prior to, during, or subsequent
to at least one administration of one or more frozen piercing
implement devices. In one embodiment 18280, the assay includes at
least one technique that includes spectroscopy, microscopy,
electrochemical detection, polynucleotide detection, histological
examination, biopsy analysis, fluorescence resonance energy
transfer, electron transfer, enzyme assay, electrical conductivity,
isoelectric focusing, chromatography, immunoprecipitation,
immunoseparation, aptamer binding, filtration, electrophoresis,
immunoassay, or radioactive assay.
In one embodiment 18310, the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation. In one embodiment 18320, the means for receiving
one or more signals includes means for receiving one or more
signals associated with selection of at least one parameter for
making or administering the at least one frozen piercing implement.
In one embodiment 18330, the at least one parameter for making the
at least one frozen piercing implement device includes one or more
of: constitution of the at least one frozen piercing implement of
the frozen piercing implement device, constitution of the at least
one frozen piercing implement device, formulation of the at least
one frozen piercing implement of the frozen piercing implement
device, formulation of the at least one frozen piercing implement
device, configuration of the at least one frozen piercing implement
of the device, configuration of the at least one frozen piercing
implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, or physical or chemical integrity
of the at least one frozen piercing implement device.
In one embodiment 18340, the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
In one embodiment 18410, the at least one agent includes one or
more of an adhesive agent, therapeutic agent, reinforcement agent,
abrasive, explosive material, or biological remodeling agent. In
one embodiment 18420, the at least one substrate includes one or
more of a cell, tissue, organ, structure, device, or food product.
In one embodiment 18430, the at least one frozen piercing implement
device includes one or more frozen piercing implements that include
at least one of hydrogen oxide, nitrogen, oxygen, air, helium,
neon, argon, xenon, chlorine, bromine, carbon dioxide, acetone,
ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane,
tetrahydrofuran, acetonitrile, acetic acid, n-butanol, isopropanol,
n-propanol, hexamethylphosphorotriamide, perfluorohydrocarbon,
methanol, ethanol, tert-butyl alcohol, formic acid, hydrogen
fluoride, ammonia, benzene, carbon tetrachloride, hexane,
dichloromethane, methylene chloride, carboxylic acid, saline,
methane, toluene, chloroform, polyethylene glycol, acetic acid,
Ringer's solution, lactated Ringer's solution, Hartmann's solution,
acetated Ringer's solution, phosphate buffered solution,
TRIS-buffered saline solution, Hank's balanced salt solution,
Earle's balanced salt solution, standard saline citrate,
HEPES-buffered saline, dextrose, glucose, or diethyl ether.
In one embodiment 18440, the output includes one or more
instructions for making the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 18450, the output includes at
least one graphical description of the at least one frozen particle
composition, frozen piercing implement, or frozen piercing
implement device. In one embodiment 18460, the user includes at
least one entity. In on embodiment 18470, the entity includes at
least one person, or computer. In one embodiment 18480, the user
readable display includes a human readable display. In one
embodiment 18490, the user readable display includes one or more
active displays. In one embodiment 18495, the user readable display
includes one or more passive displays. In one embodiment 18510, the
user readable display includes one or more of a numeric format,
graphical format, or audio format. In one embodiment 18520, the
user readable display includes one or more of a display of one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
property of the at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device. In one
embodiment 18530, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 18540, the at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement includes one or more of: constitution of the at least one
frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, or physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 18550, at least one parameter
for administering the at least one frozen particle composition or
frozen piercing implement includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
As illustrated in FIGS. 186-189, in one embodiment, a system 18600
comprises: 18610 at least one computing device; 18620 one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to receive a first
input associated with a first possible dataset, 18630 the first
possible dataset including data representative of at least one
parameter for making or administering at least one frozen particle
composition or frozen piercing implement; and 18640 one or more
instructions that when executed generate an output to a user
readable display.
In one embodiment 18650, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive parameter for making
the at least one frozen particle composition or frozen piercing
implement.
In one embodiment 18660, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the second possible dataset.
In one embodiment 18670, the at least one parameter for making the
at least one frozen particle composition or frozen piercing
implement includes one or more of: constitution of the at least one
frozen particle composition or frozen piercing implement,
formulation of the at least one frozen particle composition or
frozen piercing implement, size of the at least one frozen particle
composition or frozen piercing implement, density of the at least
one frozen particle composition or frozen piercing implement, shape
of the at least one frozen particle composition or frozen piercing
implement, physical structure of the at least one frozen particle
composition or frozen piercing implement, or physical or chemical
integrity of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 18710, at least one parameter
for administering the at least one frozen particle composition or
frozen piercing implement includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
In one embodiment 18720, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one parameter for making or administering
at least one frozen particle composition or frozen piercing
implement to at least one substrate. In one embodiment 18730, the
system further comprises one or more instructions that when
executed on the at least one computing device cause the at least
one computing device to generate at least one response support
structured on the determination.
In one embodiment 18740, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to access the first
possible dataset in response to the first input. In one embodiment
18750, the system further comprises one or more instructions that
when executed on the at least one computing device cause the at
least one computing device to generate the first possible dataset
in response to the first input. In one embodiment 18760, the system
further comprises one or more instructions that when executed on
the at least one computing device cause the at least one computing
device to determine a graphical illustration of the first possible
dataset.
In one embodiment 18810, the at least one computing device includes
one or more of a desktop computer, workstation computer, or
computing system. In one embodiment 18820, the at least one
computing system includes one or more of a cluster of processors, a
networked computer, a tablet personal computer, a laptop computer,
a mobile device, a mobile telephone, or a personal digital
assistant computer. In one embodiment 18830, the output includes
one or more instructions for making the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 18840, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement.
In one embodiment 18850, the user includes at least one entity. In
one embodiment 18860, the entity includes at least one person, or
computer. In one embodiment 18870, the user readable display
includes a human readable display. In one embodiment 18880, the
user readable display includes one or more active displays. In one
embodiment 18890, the user readable display includes one or more
passive displays.
In one embodiment 18895, the user readable display includes one or
more of a numeric format, graphical format, or audio format. In one
embodiment 18898, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the first input and at least one value related
to at least one property of the at least one frozen particle
composition or frozen piercing implement.
In one embodiment 18910, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 190-192, one embodiment includes a system
19000 comprising: 19010 circuitry for accepting a first input
associated with one or more parameters for making at least one
frozen particle composition or frozen piercing implement; 19020
circuitry for accepting a second input associated with one or more
parameters for administering at least one frozen particle
composition or frozen piercing implement to at least one substrate;
19030 circuitry for processing the first input and the second
input; and 19040 circuitry for generating an output to a user
readable display.
In one embodiment 19050, the one or more parameters for making at
least one frozen particle composition or frozen piercing implement
include at least one value derived from an image. In one embodiment
19060, the image includes a 2-dimensional or 3-dimensional image.
In one embodiment 19070, the image includes at least one image
acquired by one or more of x-ray crystallography, laser,
holography, optical coherence tomography, computer-assisted
tomography scan, computed tomography, magnetic resonance imaging,
positron-emission tomography scan, ultrasound, x-ray,
electrical-impedance monitoring, microscopy, spectrometry, flow
cytommetry, radioisotope imaging, thermal imaging, infrared
visualization, multiphoton calcium-imaging, photography, or in
silico generation.
In one embodiment 19080, the image includes at least one CAD
drawing. In one embodiment 19090, the image includes at least one
characteristic of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 19095, the at least
one characteristic includes one or more of inner diameter, outer
diameter, shape, at least one major dimension, or constitution.
In one embodiment 19110, the system further comprises circuitry for
displaying results of the processing. In one embodiment 19120, the
system further comprises circuitry for transmitting one or more
signals that include information related to the processing the
first input and the second input. In one embodiment 19130, the
system further comprises circuitry for evaluating the at least one
substrate for one or more indicators relating to one or more of:
quantitative delivery of at least one agent; depth of piercing the
at least one substrate; spatial coordinates for administration of
at least one frozen particle composition; at least one frozen
piercing implement or at least one agent; temporal coordinates for
administration of at least one frozen particle composition, at
least one frozen piercing implement, or at least one agent;
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; any
substrate response to administration of at least one frozen
piercing implement, at least one frozen particle composition, or at
least one agent.
In one embodiment 19140, the at least one agent includes at least
one therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent. In one
embodiment 19150, the output includes one or more instructions for
making the at least one frozen particle composition or frozen
piercing implement. In one embodiment 19160, the output includes at
least one graphical description of the at least one frozen particle
composition or frozen piercing implement.
In one embodiment 19170, the user includes at least one entity. In
one embodiment 19180, the entity includes at least one person, or
computer. In one embodiment 19210, the user readable display
includes a human readable display. In one embodiment 19220, the
user readable display includes one or more active displays. In one
embodiment 19230, the user readable display includes one or more
passive displays.
In one embodiment 19240, the user readable display includes one or
more of a numeric format, graphical format, or audio format. In one
embodiment 19250, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the first input and at least one value related
to at least one property of the at least one frozen particle
composition or frozen piercing implement. In one embodiment 19260,
the user readable display includes one or more of a display of one
or more differences in the comparison of at least one value related
to the second input and at least one value related to at least one
parameter for administration of the at least one frozen particle
composition or frozen piercing implement.
As illustrated in FIGS. 193-195, in one embodiment a computer
program product 19300 comprises: 19310 a recordable medium bearing
one or more instructions for accepting a first input associated
with at least one parameter for making at least one frozen particle
composition or frozen piercing implement to at least one substrate;
19320 one or more instructions for accepting a second input
associated with at least one parameter for administering the at
least one frozen particle composition or frozen piercing implement;
19330 one or more instructions for processing the first input and
the second input; and 19340 one or more instructions for generating
an output to a user readable display. In one embodiment 19350, the
recordable medium includes a computer-readable medium. In one
embodiment 19360, the recordable medium includes a communications
medium.
In one embodiment 19370, the computer program product further
comprises one or more instructions for displaying results of the
processing. In one embodiment 19380, the computer program product
further comprises one or more instructions for transmitting one or
more signals that include information related to the processing the
first input and the second input. In one embodiment 19390, the
computer program product further comprises one or more instructions
for evaluating the at least one substrate for one or more
indicators relating to one or more of: quantitative delivery of at
least one agent, depth of piercing the at least one substrate,
spatial location of delivery of at least one agent, or temporal
location of delivery of at least one agent. In one embodiment
19395, the at least one agent includes at least one therapeutic
agent, reinforcement agent, abrasive, explosive material, adhesive
agent, or biological remodeling agent.
In one embodiment 19410, the first input includes at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement includes one or more of: constitution
of the at least one frozen particle composition or frozen piercing
implement, formulation of the at least one frozen particle
composition or frozen piercing implement, configuration of the at
least one frozen particle composition or frozen piercing implement,
size of the at least one frozen particle composition or frozen
piercing implement, density of the at least one frozen particle
composition or frozen piercing implement, shape of the at least one
frozen particle composition or frozen piercing implement, physical
structure of the at least one frozen particle composition or frozen
piercing implement, or physical or chemical integrity of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 19420, the second input includes at least one
parameter for administering the at least one frozen particle
composition or frozen piercing implement includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device; velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device.
In one embodiment 19430, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 19440,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 19510, the user includes at least one entity. In
one embodiment 19520, the entity includes at least one person, or
computer. In one embodiment 19530, the user readable display
includes a human readable display. In one embodiment 19540, the
user readable display includes one or more active displays. In one
embodiment 19550, the user readable display includes one or more
passive displays. In one embodiment 19560, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 19570, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 19580, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 196-198, in one embodiment a system 19600
comprises: 19610 a recordable medium bearing one or more
instructions for accepting a first input associated with at least
one parameter for making at least one frozen particle composition
or frozen piercing implement; 19620 one or more instructions for
accepting a second input associated with at least one parameter for
administering at least one frozen particle composition or frozen
piercing implement; 19630 one or more instructions for processing
the first input and the second input; and 19640 one or more
instructions for generating an output to a user readable
display.
In one embodiment 19650 the recordable medium includes a
computer-readable medium. In one embodiment 19660, the recordable
medium includes a communications medium. In one embodiment 19670,
the system further comprises one or more instructions for
transmitting one or more signals that include information related
to the processing the first input and the second input.
In one embodiment 19680, the system further comprises one or more
instructions for evaluating the at least one substrate for one or
more indicators relating to one or more of: quantitative delivery
of at least one agent, depth of piercing the at least one
substrate, spatial location of delivery of at least one agent, or
temporal location of delivery of at least one agent. In one
embodiment 19690, the at least one agent includes at least one
therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent.
In one embodiment 19710 the first input includes at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement includes one or more of: constitution
of the at least one frozen particle composition or frozen piercing
implement, configuration of the at least one frozen particle
composition or frozen piercing implement, formulation of the at
least one frozen particle composition or frozen piercing implement,
size of the at least one frozen particle composition or frozen
piercing implement, density of the at least one frozen particle
composition or frozen piercing implement, shape of the at least one
frozen particle composition or frozen piercing implement, physical
structure of the at least one frozen particle composition or frozen
piercing implement, or physical or chemical integrity of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 19720, the second input includes at least one
parameter for administering the at least one frozen particle
composition or frozen piercing implement includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device. In one embodiment
19730, the output includes one or more instructions for making the
at least one frozen particle composition or frozen piercing
implement.
In one embodiment 19810, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 19820, the user
includes at least one entity. In one embodiment 19830, the entity
includes at least one person, or computer. In one embodiment 19840,
the user readable display includes a human readable display. In one
embodiment 19850, the user readable display includes one or more
active displays. In one embodiment 19860, the user readable display
includes one or more passive displays. In one embodiment 19870, the
user readable display includes one or more of a numeric format,
graphical format, or audio format.
In one embodiment 19880, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the first input and at least one
value related to at least one property of the at least one frozen
particle composition or frozen piercing implement. In one
embodiment 19890, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the second input and at least one value
related to at least one parameter for administration of the at
least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 199-200, in one embodiment a system 19900
comprises: 19910 at least one computer program, configured with a
computer-readable medium, for use with at least one computer system
and wherein the computer program includes a plurality of
instructions including but not limited to: one or more instructions
for accepting a first input associated with one or more parameters
for making one or more frozen particle compositions or frozen
piercing implements to at least one substrate; one or more
instructions for accepting a second input associated with one or
more parameters for administering one or more frozen particle
compositions or frozen piercing implements; one or more
instructions for processing the first input and the second input;
and one or more instructions for generating an output to a user
readable display.
In one embodiment 19920, the system further comprises one or more
instructions for transmitting one or more signals that include
information related to the processing the first input and the
second input. In one embodiment 19930, the system further comprises
one or more instructions for evaluating the at least one biological
tissue for one or more indicators relating to one or more of:
quantitative delivery of at least one agent, depth of piercing the
at least one substrate, spatial location of delivery of at least
one agent, or temporal location of delivery of at least one
agent.
In one embodiment 19940, the at least one agent includes at least
one therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent. In one
embodiment 19950, the system further comprises at least one
computing device. In one embodiment 19960, the at least one
computing device is configured to communicate with at least one
printing device, at least one imaging device, or at least one input
device.
In one embodiment 19970, the first input includes at least one
parameter for making the at least one frozen piercing implement
device includes one or more of: constitution of the at least one
frozen piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, or physical or chemical integrity of the at least
one frozen piercing implement device.
In one embodiment 20010, the first input includes at least one
parameter for making the at least one frozen particle composition
or frozen piercing implement includes one or more of: constitution
of the at least one frozen particle composition or frozen piercing
implement, configuration of the at least one frozen particle
composition or frozen piercing implement, formulation of the at
least one frozen particle composition or frozen piercing implement,
size of the at least one frozen particle composition or frozen
piercing implement, density of the at least one frozen particle
composition or frozen piercing implement, shape of the at least one
frozen particle composition or frozen piercing implement, physical
structure of the at least one frozen particle composition or frozen
piercing implement, or physical or chemical integrity of the at
least one frozen particle composition or frozen piercing
implement.
In one embodiment 20020, the second input includes at least one
parameter for administering the at least one frozen particle
composition or frozen piercing implement includes one or more of:
substrate type; substrate function; substrate size; substrate
constitution; substrate architecture; substrate durability;
substrate temperature; temperature of administration conditions;
depth of administration of the at least one frozen particle
composition or frozen piercing implement; substrate source; one or
more temporal coordinates; one or more spatial coordinates;
presence or absence of at least one agent; presence or absence of
at least one microparticle, nanoparticle, lens, tunablelens,
sensor, transducer, actuator, detector, heater, valve, gate,
channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit; angle of
administration of the at least one frozen piercing implement
device; force of administration of the at least one frozen piercing
implement device; velocity of administration of the at least one
frozen piercing implement device; quantity of frozen piercing
implements of the device; quantity of frozen piercing implement
devices administered; rate of administration of more than one
frozen piercing implement devices; method of administration of at
least one frozen piercing implement device; timing of
administration of at least one frozen piercing implement; or rate
of delivery of at least one agent of the device.
In one embodiment 20030, the second input includes at least one
parameter for administering at least one frozen piercing implement
device to at least one substrate includes one or more of: substrate
type; substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
As illustrated in FIGS. 201-204, a system 20100, comprises: 20110
at least one computing device; 20120 one or more instructions that
when executed on the at least one computing device cause the at
least one computing device to receive a first input associated with
a first possible dataset, 20130 the first possible dataset
including data representative of at least one parameter for making
or administering at least one frozen particle composition, frozen
piercing implement, or frozen piercing implement device to at least
one substrate; and 20140 one or more instructions for generating an
output to a user readable display.
In one embodiment 20150, the at least one frozen piercing implement
device includes at least one frozen piercing implement array
device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 20160, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
In one embodiment 20170, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to compare a value
associated with the first possible dataset with a second dataset
including values of at least one predictive parameter for
administering at least one frozen particle compositions or frozen
piercing implements to at least one substrate. In one embodiment
20180, the first input includes at least one parameter for making
the at least one frozen piercing implement device includes one or
more of: constitution of the at least one frozen piercing implement
of the frozen piercing implement device, constitution of the at
least one frozen piercing implement device, configuration of the at
least one frozen piercing implement or frozen piercing implement
device, formulation of the at least one frozen piercing implement
of the frozen piercing implement device, formulation of the at
least one frozen piercing implement device, size of the at least
one frozen piercing implement of the frozen piercing implement
device, size of the at least one frozen piercing implement device,
shape of the at least one frozen piercing implement of the frozen
piercing implement device, shape of the at least one frozen
piercing implement device, physical structure of the at least one
frozen piercing implement of the frozen piercing implement device,
physical structure of the at least one frozen piercing implement
device, physical or chemical integrity of the at least one frozen
piercing implement of the frozen piercing implement device, or
physical or chemical integrity of the at least one frozen piercing
implement device.
In one embodiment 20210, the second input includes at least one
parameter for administering at least one frozen piercing implement
device to at least one substrate includes one or more of: substrate
type; substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
In one embodiment 20220, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the second possible dataset. In one
embodiment 20230, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine from
the comparison at least one parameter for administering at least
one frozen particle composition, frozen piercing implement, or
frozen piercing implement device to at least one substrate.
In one embodiment 20240, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate at least
one response support structured on the determination.
In one embodiment 20250, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to access the first
possible dataset in response to the first input.
In one embodiment 20310, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to generate the
first possible dataset in response to the first input. In one
embodiment 20320, the system further comprises one or more
instructions that when executed on the at least one computing
device cause the at least one computing device to determine a
graphical illustration of the first possible dataset. In one
embodiment 20330, the at least one computing device includes one or
more of a desktop computer, workstation computer, or computing
system.
In one embodiment 20340, the at least one computing system includes
one or more of a cluster of processors, a networked computer, a
tablet personal computer, a laptop computer, a mobile device, a
mobile telephone, or a personal digital assistant computer. In one
embodiment 20350, the output includes one or more instructions for
making the at least one frozen particle composition or frozen
piercing implement. In one embodiment 20360, the output includes at
least one graphical description of the at least one frozen particle
composition or frozen piercing implement.
In one embodiment 20370, the user includes at least one entity. In
one embodiment 20380, the entity includes at least one person, or
computer. In one embodiment 20390, the user readable display
includes a human readable display. In one embodiment 20410, the
user readable display includes one or more active displays. In one
embodiment 20420, the user readable display includes one or more
passive displays. In one embodiment 20430, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 20440, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 20450, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 205-208, a system 20500 comprises: 20510
circuitry for accepting a first input associated with at least one
parameter for making at least one frozen piercing implement device;
20520 circuitry for accepting a second input associated with at
least one parameter for administering at least one frozen piercing
implement device to at least one substrate; 20530 circuitry for
processing the first input and the second input; and 20540
circuitry for generating an output to a user readable display. In
one embodiment 20550, the at least one frozen piercing implement
device includes at least one frozen piercing implement array
device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 20560, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device. In one embodiment 20570,
the first input includes at least one value derived from at least
one image. In one embodiment 20580, the at least one image includes
at least one 2-dimensional or 3-dimensional image. In one
embodiment 20590, the image includes at least one image acquired by
one or more of x-ray crystallography, laser, holography, optical
coherence tomography, computer-assisted tomography scan, computed
tomography, magnetic resonance imaging, positron-emission
tomography scan, ultrasound, x-ray, electrical-impedance
monitoring, microscopy, spectrometry, flow cytommetry, radioisotope
imaging, thermal imaging, infrared visualization, multiphoton
calcium-imaging, photography, or in silico generation.
In one embodiment 20610, the at least one image includes at least
one CAD drawing. In one embodiment 20620, the at least one image
includes at least one characteristic of the at least one frozen
piercing implement of the device or the frozen piercing implement
device. In one embodiment 20630, the at least one characteristic of
the one or more frozen piercing implement device includes one or
more of number of frozen piercing implements, number of total
piercing implements, size of at least one frozen piercing
implement, constitution of at least one frozen piercing implement,
shape of at least one frozen piercing implement, shape of the
device, configuration of the device, spacing of at least two
components of the device, spacing of at least two frozen piercing
implements of the device, or presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit.
In one embodiment 20640, the first input includes at least one
parameter for making the at least one frozen piercing implement
device includes one or more of: constitution of the at least one
frozen piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunablelens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, power source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
In one embodiment 20710, the second input includes at least one
parameter for administering the at least one frozen piercing
implement device includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
In one embodiment 20720, the system further comprises circuitry for
transmitting one or more signals that include information related
to the processing the first input and the second input. In one
embodiment 20730, the system further comprises circuitry for
evaluating the at least one substrate for one or more indicators
relating to one or more of: quantitative delivery of at least one
agent, depth of piercing the at least one substrate, spatial
location of delivery of at least one agent, or temporal location of
delivery of at least one agent. In one embodiment 20740, the at
least one agent includes at least one therapeutic agent,
reinforcement agent, abrasive, explosive material, adhesive agent,
or biological remodeling agent. In one embodiment 20750, the output
includes one or more instructions for making the at least one
frozen particle composition or frozen piercing implement. In one
embodiment 20760, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement.
In one embodiment 20810, the user includes at least one entity. In
one embodiment 20820, the entity includes at least one person, or
computer. In one embodiment 20830, the user readable display
includes a human readable display. In one embodiment 20840, the
user readable display includes one or more active displays. In one
embodiment 20850, the user readable display includes one or more
passive displays. In one embodiment 20860, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 20870, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 20880, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
As illustrated in FIGS. 209-211, a computer program product 20900
comprises: 20910 a recordable medium bearing one or more
instructions for accepting a first input associated with at least
one parameter for making at least one frozen piercing implement
device; 20920 one or more instructions for accepting a second input
associated with at least one parameter for administering the at
least one frozen piercing implement device to at least one
substrate; 20930 one or more instructions for processing the first
input and the second input; and 20940 one or more instructions for
generating an output to a user readable display.
In one embodiment 20950 the recordable medium includes a
computer-readable medium. In one embodiment 20960 the recordable
medium includes a communications medium. In one embodiment 20970
the computer program product further comprises one or more
instructions for displaying results of the processing. In one
embodiment 20980 the computer program product further comprises one
or more instructions for transmitting one or more signals that
include information related to the processing the first input and
the second input. In one embodiment 20990 the first input includes
at least one parameter for making the at least one frozen piercing
implement device includes one or more of: constitution of the at
least one frozen piercing implement of the frozen piercing
implement device, constitution of the at least one frozen piercing
implement device, configuration of the at least one frozen piercing
implement or frozen piercing implement device, formulation of the
at least one frozen piercing implement of the frozen piercing
implement device, formulation of the at least one frozen piercing
implement device, size of the at least one frozen piercing
implement of the frozen piercing implement device, size of the at
least one frozen piercing implement device, shape of the at least
one frozen piercing implement of the frozen piercing implement
device, shape of the at least one frozen piercing implement device,
physical structure of the at least one frozen piercing implement of
the frozen piercing implement device, physical structure of the at
least one frozen piercing implement device, physical or chemical
integrity of the at least one frozen piercing implement of the
frozen piercing implement device, physical or chemical integrity of
the at least one frozen piercing implement device, or presence or
absence of at least one microparticle, nanoparticle, lens,
tunablelens, sensor, transducer, actuator, detector, heater, valve,
gate, channel, detection material, pump, power source, injector,
controller, receiver, transmitter, or circuit, in the at least one
frozen piercing implement or frozen piercing implement device.
In one embodiment 21010, the at least one parameter for
administering at least one frozen piercing implement device to at
least one substrate includes one or more of: substrate type;
substrate function; substrate size; substrate constitution;
substrate architecture; substrate durability; substrate
temperature; temperature of administration conditions; depth of
administration of the at least one frozen particle composition or
frozen piercing implement; substrate source; one or more temporal
coordinates; one or more spatial coordinates; presence or absence
of at least one agent; presence or absence of at least one
microparticle, nanoparticle, lens, tunablelens, sensor, transducer,
actuator, detector, heater, valve, gate, channel, detection
material, pump, power source, injector, controller, receiver,
transmitter, or circuit; angle of administration of the at least
one frozen piercing implement device; force of administration of
the at least one frozen piercing implement device; velocity of
administration of the at least one frozen piercing implement
device; quantity of frozen piercing implements of the device;
quantity of frozen piercing implement devices administered; rate of
administration of more than one frozen piercing implement devices;
method of administration of at least one frozen piercing implement
device; timing of administration of at least one frozen piercing
implement; or rate of delivery of at least one agent of the
device.
In one embodiment 21020, the computer program product further
comprises one or more instructions for evaluating the at least one
substrate for one or more indicators relating to one or more of:
quantitative delivery of at least one agent, depth of piercing the
at least one substrate, spatial location of delivery of at least
one agent, or temporal location of delivery of at least one agent.
In one embodiment 21030, the at least one agent includes at least
one therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent. In one
embodiment 21040, the at least one frozen piercing implement device
includes at least one frozen piercing implement array device,
frozen piercing implement fluidic device, or frozen piercing
implement injection device. In one embodiment 21050, the frozen
piercing implement injection device includes a frozen piercing
implement auto-injection device. In one embodiment 21060, the
output includes one or more instructions for making the at least
one frozen particle composition or frozen piercing implement.
In one embodiment 21110, the output includes at least one graphical
description of the at least one frozen particle composition or
frozen piercing implement. In one embodiment 21120, the user
includes at least one entity. In one embodiment 21130, the entity
includes at least one person, or computer. In one embodiment 21140,
the user readable display includes a human readable display. In one
embodiment 21150, the user readable display includes one or more
active displays. In one embodiment 21160, the user readable display
includes one or more passive displays. In one embodiment 21170, the
user readable display includes one or more of a numeric format,
graphical format, or audio format. In one embodiment 21180, the
user readable display includes one or more of a display of one or
more differences in the comparison of at least one value related to
the first input and at least one value related to at least one
property of the at least one frozen particle composition or frozen
piercing implement. In one embodiment 21190, the user readable
display includes one or more of a display of one or more
differences in the comparison of at least one value related to the
second input and at least one value related to at least one
parameter for administration of the at least one frozen particle
composition or frozen piercing implement.
As illustrated in FIGS. 212-214, a system 21200 comprises: 21210 a
recordable medium bearing one or more instructions for accepting a
first input associated with at least one parameter for making at
least one frozen piercing implement device; 21220 one or more
instructions for accepting a second input associated with at least
one parameter for administering at least one frozen piercing
implement device; 21230 one or more instructions for processing the
first input and the second input; and 21240 one or more
instructions for generating an output to a user readable display.
In one embodiment 21250, the at least one frozen piercing implement
device includes at least one frozen piercing implement array
device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 21260, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
In one embodiment 21270, the recordable medium includes a
computer-readable medium. In one embodiment 21280, the recordable
medium includes a communications medium. In one embodiment 21290,
the system further comprises one or more instructions for
transmitting one or more signals that include information related
to the processing the first input and the second input. In one
embodiment 21310, the first input includes at least one parameter
for making the at least one frozen piercing implement device
includes one or more of: constitution of the at least one frozen
piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunablelens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, power source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
In one embodiment 21320, the second input includes at least one
parameter for administering the at least one frozen piercing
implement device includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
In one embodiment 21410, the system further comprises one or more
instructions for evaluating the at least one substrate for one or
more indicators relating to one or more of: quantitative delivery
of at least one agent, depth of piercing the at least one
substrate, spatial location of delivery of at least one agent, or
temporal location of delivery of at least one agent. In one
embodiment 21420, the at least one agent includes at least one
therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent. In one
embodiment 21430, the output includes one or more instructions for
making the at least one frozen particle composition or frozen
piercing implement. In one embodiment 21440, the output includes at
least one graphical description of the at least one frozen particle
composition or frozen piercing implement.
In one embodiment 21450, the user includes at least one entity. In
one embodiment 21460, the entity includes at least one person, or
computer. In one embodiment 21470, the user readable display
includes a human readable display. In one embodiment 21480, the
user readable display includes one or more active displays. In one
embodiment 21485, the user readable display includes one or more
passive displays.
In one embodiment 21490, the user readable display includes one or
more of a numeric format, graphical format, or audio format. In one
embodiment 21495, the user readable display includes one or more of
a display of one or more differences in the comparison of at least
one value related to the first input and at least one value related
to at least one property of the at least one frozen particle
composition or frozen piercing implement. In one embodiment 21498,
the user readable display includes one or more of a display of one
or more differences in the comparison of at least one value related
to the second input and at least one value related to at least one
parameter for administration of the at least one frozen particle
composition or frozen piercing implement.
As illustrated in FIGS. 215-218, a system 21500 comprises: 21510 at
least one computer program, configured with a computer-readable
medium, for use with at least one computer system and wherein the
computer program includes a plurality of instructions including but
not limited to: one or more instructions for accepting a first
input associated with at least one parameter for making at least
one frozen piercing implement device; one or more instructions for
accepting a second input associated with at least one parameter for
administering at least one frozen piercing implement device; one or
more instructions for processing the first input and the second
input; and one or more instructions for generating an output to a
user readable display. In one embodiment 21520, the system further
comprises one or more instructions for transmitting one or more
signals that include information related to the processing the
first input and the second input. In one embodiment 21530, the
system further comprises one or more instructions for evaluating
the at least one biological tissue for one or more indicators
relating to one or more of: quantitative delivery of at least one
agent, depth of piercing the at least one substrate, spatial
location of delivery of at least one agent, or temporal location of
delivery of at least one agent.
In one embodiment 21540, the at least one agent includes at least
one therapeutic agent, reinforcement agent, abrasive, explosive
material, adhesive agent, or biological remodeling agent. In one
embodiment 21650, the system further comprises at least one
computing device. In one embodiment 21660, the at least one
computing device is configured to communicate with at least one
printing device, at least one imaging device, or at least one input
device. In one embodiment 21670, the at least one frozen piercing
implement device includes at least one frozen piercing implement
array device, frozen piercing implement fluidic device, or frozen
piercing implement injection device. In one embodiment 21680, the
frozen piercing implement injection device includes a frozen
piercing implement auto-injection device.
In one embodiment 21710, the output includes one or more
instructions for making the at least one frozen particle
composition or frozen piercing implement. In one embodiment 21720,
the output includes at least one graphical description of the at
least one frozen particle composition or frozen piercing implement.
In one embodiment 21730, the user includes at least one entity. In
one embodiment 21740, the entity includes at least one person, or
computer. In one embodiment 21750, the user readable display
includes a human readable display. In one embodiment 21760, the
user readable display includes one or more active displays. In one
embodiment 21770, the user readable display includes one or more
passive displays. In one embodiment 21780, the user readable
display includes one or more of a numeric format, graphical format,
or audio format. In one embodiment 21790, the user readable display
includes one or more of a display of one or more differences in the
comparison of at least one value related to the first input and at
least one value related to at least one property of the at least
one frozen particle composition or frozen piercing implement. In
one embodiment 21795, the user readable display includes one or
more of a display of one or more differences in the comparison of
at least one value related to the second input and at least one
value related to at least one parameter for administration of the
at least one frozen particle composition or frozen piercing
implement.
In one embodiment 21810, the first input includes at least one
parameter for making the at least one frozen piercing implement
device includes one or more of: constitution of the at least one
frozen piercing implement of the frozen piercing implement device,
constitution of the at least one frozen piercing implement device,
configuration of the at least one frozen piercing implement or
frozen piercing implement device, formulation of the at least one
frozen piercing implement of the frozen piercing implement device,
formulation of the at least one frozen piercing implement device,
size of the at least one frozen piercing implement of the frozen
piercing implement device, size of the at least one frozen piercing
implement device, shape of the at least one frozen piercing
implement of the frozen piercing implement device, shape of the at
least one frozen piercing implement device, physical structure of
the at least one frozen piercing implement of the frozen piercing
implement device, physical structure of the at least one frozen
piercing implement device, physical or chemical integrity of the at
least one frozen piercing implement of the frozen piercing
implement device, physical or chemical integrity of the at least
one frozen piercing implement device, or presence or absence of at
least one microparticle, nanoparticle, lens, tunablelens, sensor,
transducer, actuator, detector, heater, valve, gate, channel,
detection material, pump, power source, injector, controller,
receiver, transmitter, or circuit, in the at least one frozen
piercing implement or frozen piercing implement device.
In one embodiment 21820, the second input includes at least one
parameter for administering the at least one frozen piercing
implement device includes one or more of: substrate type; substrate
function; substrate size; substrate constitution; substrate
architecture; substrate durability; substrate temperature;
temperature of administration conditions; depth of administration
of the at least one frozen particle composition or frozen piercing
implement; substrate source; one or more temporal coordinates; one
or more spatial coordinates; presence or absence of at least one
agent; presence or absence of at least one microparticle,
nanoparticle, lens, tunablelens, sensor, transducer, actuator,
detector, heater, valve, gate, channel, detection material, pump,
power source, injector, controller, receiver, transmitter, or
circuit; angle of administration of the at least one frozen
piercing implement device; force of administration of the at least
one frozen piercing implement device; velocity of administration of
the at least one frozen piercing implement device; quantity of
frozen piercing implements of the device; quantity of frozen
piercing implement devices administered; rate of administration of
more than one frozen piercing implement devices; method of
administration of at least one frozen piercing implement device;
timing of administration of at least one frozen piercing implement;
or rate of delivery of at least one agent of the device.
The foregoing detailed description has set forth various
embodiments of the devices and/or processes via the use of block
diagrams, flowcharts, and/or examples. Insofar as such block
diagrams, flowcharts, and/or examples contain one or more functions
and/or operations, it will be understood by those within the art
that each function and/or operation within such block diagrams,
flowcharts, or examples can be implemented, individually and/or
collectively, by a wide range of hardware, software, firmware, or
virtually any combination thereof. In one embodiment, several
portions of the subject matter described herein can be implemented
via Application Specific Integrated Circuits (ASICs), Field
Programmable Gate Arrays (FPGAs), digital signal processors (DSPs),
or other integrated formats. However, those skilled in the art will
recognize that some aspects of the embodiments disclosed herein, in
whole or in part, can be equivalently implemented in integrated
circuits, as one or more computer programs running on one or more
computers (e.g., as one or more programs running on one or more
computer systems), as one or more programs running on one or more
processors (e.g., as one or more programs running on one or more
microprocessors), as firmware, or as virtually any combination
thereof, and that designing the circuitry and/or writing the code
for the software and or firmware would be well within the skill of
one of skill in the art in light of this disclosure. In addition,
those skilled in the art will appreciate that the mechanisms of the
subject matter described herein are capable of being distributed as
a program product in a variety of forms, and that an illustrative
embodiment of the subject matter described herein applies
regardless of the particular type of signal bearing medium used to
actually carry out the distribution. Examples of a signal bearing
medium include, but are not limited to, the following: a recordable
type medium such as a floppy disk, a hard disk drive, a Compact
Disc (CD), a Digital Video Disk (DVD), a digital tape, a computer
memory, etc.; and a transmission type medium such as a digital
and/or an analog communication medium (e.g., a fiber optic cable, a
waveguide, a wired communications link, a wireless communication
link (e.g., transmitter, receiver, transmission logic, reception
logic, etc.), etc.).
For any of the various aspects and embodiments disclosed herein,
one or more kits can be developed with the components described
herein. In one embodiment, a kit includes one or more frozen
particle compositions as described herein. In one embodiment, a kit
includes one or more frozen particle compositions and at least one
therapeutic agent as disclosed herein. In one embodiment, a kit
includes one or more frozen particle compositions and one or more
reinforcement agents. In one embodiment, a kit includes one or more
frozen particle compositions and one or more explosive
materials.
PROPHETIC EXAMPLES
Example 1
Compositions and Methods of Making Frozen Particles
Frozen particle compositions suitable for various embodiments
described herein can be produced by controlling the pressure and
temperature of hydrogen oxide that is introduced as a liquid, gas
or solid. Frozen particle compositions, including frozen hydrogen
oxide ice Ic, are produced by cooling small hydrogen oxide droplets
(.about.6 .mu.m diameter) below approximately -38.degree. C. (See
e.g., Murray, et al., Phys. Chem. Chem. Phys. vol. 8, pp. 186-192
(2006), which is incorporated herein by reference). Emulsions of
30-40% by weight of distilled and de-ionized hydrogen oxide in
paraffin oil (Fisher Scientific) are agitated to produce hydrogen
oxide droplets of mean diameters ranging from 5 to 35 .mu.m as
determined by optical microscopy. The droplets are cooled to
approximately -100.degree. C. at a rate of approximately 10.degree.
C./min by using a cryostat cooled with liquid nitrogen and
containing a heater and temperature controller. Freezing liquid
droplets with a median diameter of approximately 5.6 .mu.m or
smaller can provide approximately 80% frozen ice Ic and
approximately 20% frozen ice 1h. Following the procedures of Murray
et al, selective production of ice Ic in pellet form produces
quantities suitable for use in various embodiments described
herein.
Frozen particles generated in this manner are utilized for abrasion
of at least one biological tissue, including but not limited to
skin. The frozen particle composition is administered to at least
one biological tissue by, for example, accelerating, ejecting, or
propelling the frozen particles by way of a carrier gas under
pressure (e.g., air, carbon dioxide, nitrogen, neon, argon, etc.)
through a tube, or other device directed toward at least one
biological tissue, such as skin. Microdermabrasion,
microscissuining, or other surface abrasion techniques are carried
out in a similar fashion.
Example 2
Compositions and Methods of Making Frozen Particles
Frozen particles, including frozen hydrogen oxide ice Ic, are
produced by depositing hydrogen oxide vapor onto a copper plate
held at low temperatures in vacuo. Purified (deionized) hydrogen
oxide is added to a vessel at approximately 25.degree. C. and the
hydrogen oxide vapor is condensed onto a metal plate held at
approximately -196.degree. C. in vacuo. The deposited amorphous ice
is heated (at 10.degree. C./min) to approximately -93.degree. C.
and is converted to crystalline cubic ice (ice Ic). Ice Ic is
stable when stored under liquid nitrogen (See e.g., Johari, et al.,
J. Phys. Chem., vol. 94, pp. 1212-1214 (1990), which is
incorporated herein by reference). An example of an apparatus that
is used to produce frozen hydrogen oxide ice Ic is described in
Hallbrucker et al (J. Phys. Chem., vol. 93, pp. 4986-4990 (1989),
which is incorporated herein by reference).
Example 3
Compositions and Methods of Making Frozen Particles
Frozen hydrogen oxide ice Ic particles are produced from small
hydrogen oxide droplets in an example of a "pelletizer" apparatus
similar to those described by, for example, U.S. Pat. No.
4,617,064; or 6,306,119, each of which is incorporated herein by
reference. Frozen hydrogen oxide ice Ic particles are formed by
spraying hydrogen oxide droplets of the desired size into a
compartment filled with a cold inert gas maintained at the desired
temperature, for example, nitrogen gas maintained at approximately
-100.degree. C. to promote formation of ice Ic. Spray droplet size
is maintained by variation of nozzle/aperture size and hydrogen
oxide pressure to yield droplet diameters ranging from nanometers
to centimeters. Frozen hydrogen oxide ice Ic, ice Ih, amorphous low
density ice, amorphous high density ice, and other forms are
produced by controlling the temperature and pressure of the
compartment. Cubic hydrogen oxide ice Ic particles are formed in a
step-wise process, by maintaining the chamber at a very low
temperature (approximately -196.degree. C.) with increased
pressure, which first promotes formation of amorphous hydrogen
oxide ice. Next, the chamber is heated to approximately -93.degree.
C., which results in transformation to cubic hydrogen oxide ice
(ice Ic) particles.
The hydrogen oxide ice particles are propelled into a delivery
system (such as tubing and nozzle) by nitrogen gas under pressure.
The delivery system is maintained at the appropriate temperature
for preservation of the hydrogen oxide particle structure, (e.g.,
approximately -93.degree. C. for ice Ic structure).
Example 4
Compositions and Methods of Making Frozen Carbon Dioxide
Particles
Carbon dioxide frozen particles are produced from small carbon
dioxide droplets in a "pelletizer" similar to those described by,
for example, U.S. Pat. Nos. 4,617,064; and 6,306,119; each of which
is incorporated herein by reference. Carbon dioxide frozen
particles are formed by spraying liquid carbon dioxide droplets
into a compartment maintained at low temperatures (e.g.,
approximately -100.degree. C.). Droplet size is regulated by
varying nozzle or aperture size, and pressure. Carbon dioxide
droplet diameters range, for example, from nanometers to
centimeters. The frozen carbon dioxide particles are propelled into
a delivery system (e.g., tubing and nozzle) by carrier gas, (e.g.,
air or nitrogen) under pressure. The carbon dioxide particles are
maintained while in the delivery system at the appropriate
temperature, (e.g., approximately -100.degree. C.). Frozen carbon
dioxide particles sublimate, or transition to a gas phase, at
approximately -78.5.degree. C. and 1 atm pressure.
Example 5
Compositions and Methods of Making Frozen DMSO Particles
Dimethyl sulfoxide (DMSO) frozen particles are produced from DMSO
droplets. for example, in a "pelletizer" apparatus similar to those
described by, for example. U.S. Pat. Nos. 4,617,064; 6,306,119,
each of which is incorporated herein by reference. DMSO frozen
particles are formed from spraying liquid DMSO droplets of the
desired size into a compartment that is maintained at low
temperature, for example, less than approximately 18.5.degree. C.
Droplet size is regulated by varying nozzle or aperture size, and
DMSO pressure, with compressed air as a carrier gas. DMSO droplet
diameters range, for example, from nanometers to centimeters. The
DMSO frozen particles are propelled by a carrier gas (e.g., air or
nitrogen) under pressure to enter a delivery system (e.g., tubing
and nozzle). In order to preserve DMSO particle structure, the
delivery system is maintained at low temperature (e.g., less than
approximately 18.5.degree. C.).
Example 6
Methods of Assessment or Selection of Frozen Particles
According to various embodiments described herein, at least one
frozen particle is made by lowering the temperature of liquid
droplets of a selected material. Droplet and particle sizes are
measured by imaging a spray or particle stream upon a background
screen. The background screen is illuminated with a short pulse of
light, for example, from an infrared laser beam (at approximately
805 nm), which is capable of pulsing at frequencies of
approximately 1000 Hz.
A digital camera captures high resolution images of the droplets or
particles. High-speed, real-time particle sizing software analyses
the images to assess the diameter distribution for the particles
and to determine the shape. The diameter of each droplet is
determined automatically by referencing the number of dark pixels
in the droplet image to the pixel area of a calibration circle.
Droplet diameters between approximately 100 m (.+-.3.2%) and
approximately 2000 m (.+-.0.03%) were measured with 95% confidence
(See e.g., Ireland et al., 6th ASME-JSME Thermal Engineering Joint
Conference (2003), which is incorporated herein by reference).
Instruments, computer programs and protocols for measuring particle
and droplet size are available, for example, from Oxford Lasers,
Shirley, MA.
Example 7
Methods of Assessment or Selection of Frozen Particles
According to various embodiments described herein, at least one
frozen particle is made by lowering the temperature of liquid
droplets of a selected material. Droplet and particle sizes are
measured by laser diffraction. Laser diffraction based particle
size analysis relies on particles passing through a laser beam and
scattering light at an angle that is directly related to their
size. As particle size decreases, the observed scattering angle
increases logarithmically. Scattering intensity is also dependent
on particle size, and decreases with decreasing particle volume.
Thus, large particles scatter light at narrow angles with high
intensity whereas small particles scatter at wider angles but with
low intensity. Laser diffraction is used for the non-destructive
analysis of wet or dry samples, to measure particles in the size
range 0.02 to 2000 micrometers A laser diffraction instrument,
protocols and analysis software are available, for example, from
Malvern Instruments Ltd. (Malvern, Worcestershire, WR14 1XZ United
Kingdom).
Example 8
Compositions and Methods of Making Frozen Particles Including a
Reinforcement Agent
One or more reinforcement agents are added to the frozen particles
during the formation process. Among other things, reinforcement
agents can increase the strength of frozen particles (e.g.,
increase the modulus of rupture of ice) and decrease the
deformation of frozen particles (e.g., decrease the beam deflection
of ice). As indicated in Table A below, glass fibers present at 9%
(wt./vol.), for example, increase the modulus of rupture of ice by
approximately 7-fold relative to ice derived from unreinforced
hydrogen oxide ice (See e.g., Kingery, Science, vol. 134, pp.
164-168 (1960), which is incorporated herein by reference).
TABLE-US-00005 TABLE A Strength of fresh ice with sawdust and
Fiberglass, respectively, added. Modulus of rupture (kg/cm.sup.2)
Addition (%) Sawdust (-17.degree. C.) Fiberglass (-20.degree. C.) 0
22.5 24.1 0.8 22.7 24.0 2.5 35 65.4 9.0 60 161 14.0 66.7 N/A
Additions were % wt./vol. (Kingery, Ibid).
As indicated in FIG. 5, the beam deflection is less than 0.005
inches for hydrogen oxide ice that is reinforced with approximately
9.0% glass fibers and increases over time for hydrogen oxide ice
that is reinforced with approximately 0.8% glass fibers (Kingery,
Ibid). Furthermore, hydrogen oxide ice with approximately 9% (w/v)
of glass fibers is not deformed over 23 hours under an applied
force of approximately 24.5 in.lbs. As described in Kingery, et al,
and as indicated in FIG. 5, beam deflection of hydrogen oxide ice
with approximately 0.8% glass fibers is approximately 0.16 inches
after 23 hours under 25.3 inlbs. of force. Likewise, as indicated
in FIG. 5, and according to Kingery et al, hydrogen oxide ice
without reinforcement agents is deformed approximately 0.05 inches
after 4 hours under approximately 26.6 inlbs. of force.
Additionally, aluminum and silica carbonate particles can be mixed
at various volume fractions and co-milled under an argon atmosphere
to produce nanocrystalline composites as reinforcement agents for
frozen particle compositions. (See e.g., Kamrani, et al., Powder
Met. vol. 50, pp. 276-282(7) (2007), which is incorporated herein
by reference).
Example 9
Compositions and Methods of Making Frozen Particles
Frozen particles (e.g., carbon dioxide, DMSO, gelatin) are
reinforced by incorporating one or more reinforcement agents,
including but not limited to silica beads, fiberglass, polyethylene
glycol, kaolin, or wood fibers.
Silica beads approximately 1 micrometer in diameter are mixed with
hydrogen oxide at approximately 0.degree. C. to make volume
fractions including the approximate ranges, but not limited to, 0,
0.004, 0.04, 0.15, 0.29, 0.49 and 0.63 volume fraction. The volume
fractions, or one or more particular volume fraction, are frozen
in, for example, a cylindrical mold, at low temperatures (e.g.,
approximately -10.degree. C.). Unconfined coaxial compression tests
are used to determine the maximum stress (also known as the failure
point) of the one or more frozen particles at defined temperatures
and strain rates (See e.g., Yasui et al, Geophys. Res. Lett., vol.
35, L12206, (2008), which is incorporated herein by reference).
As indicated in FIG. 6, maximum stress. values (MPa) increase for
mixtures with an increased volume fraction of silica beads relative
to the maximum stress for unreinforced hydrogen oxide ice. (See
e.g., Yasui et al, Ibid.) .phi.=silica volume fraction
The strength of specific frozen particles is altered by varying the
composition of frozen particle mixtures containing one or more
reinforcement agents. For example, Table B indicates the frozen
particle strength of frozen particles including hydrogen oxide,
DMSO, carbon dioxide, and gelatin, which contain at least one
reinforcement agent. As indicated, the reinforced frozen particles
exhibited increased strength compared to their unreinforced
counterparts. As indicated in Table B, frozen particles containing
at least one reinforcement agent at the volume fractions shown in
the table displayed maximal strength in compression tests. (See
also, FIGS. 5 and 6, as well as Table A herein for hydrogen oxide
frozen particle strength).
TABLE-US-00006 TABLE B Frozen particles and reinforcement agents
leading to increased particle strength Particle Base Fiber Glass
Saw Dust Silica Beads PEG Kaolin Ice 0.15* 0.14 0.63 ND 0.15 DMSO
0.15 0.14 0.63 ND 0.15 carbon 0.15 0.14 0.63 ND 0.15 dioxide
gelatin 0.15 0.14 0.63 ND 0.15 Volume fraction for reinforcement
agents in frozen particle base materials is given. ND = Not
Determined. (Yasui, et al.)
Example 10
Vaccine Compositions and Methods of Making Frozen Particles
As described herein, immunization of a subject with a vaccine is
accomplished by way of introduction of the vaccine through, for
example, subcutaneous, transcutaneous or intramuscular
administration. (See e.g., Berzofsky et al, Nat. Rev. Immunol. vol.
1, pp. 209-219, (2001), which is incorporated herein by reference).
Non-limiting examples of frozen particle vaccines are described
herein, and include one or more immunogens. The immunogen
therapeutic compositions are made, for example, in solution or as a
solid in suspension or as a colloid created from, for example,
buffered solutions (e.g., phosphate, citrate, lactate, pyruvate or
an organic acid buffer) that optimize the stability and
immunogenicity of the vaccine.
Storage stability of vaccines depends upon many factors, including
vaccine formulation and storage temperature. For example, an
influenza subunit vaccine formulated with trehalose, and Hepes
buffered saline, is stable at room temperature for approximately 26
weeks (See e.g., Amorij et al, Pharm. Res. vol. 25, pp. 1256-1273
(2008), which is incorporated herein by reference).
Vaccines with adjuvants such as: N-acetyl
muramyl-1-alanyl-d-isoglutamine, also called muramyl dipeptide
(MDP) or monophosphoryl lipid A (MPL) elicit enhanced cellular and
humoral immunity (See e.g., Aguilar et al Vaccine vol. 25, pp.
3752-62 (2007), which is incorporated herein by reference).
Furthermore, stable genetic transformation and vaccination of
intact plant cells has been achievable by particle bombardment
processes (See e.g., Klein et al PNAS vol. 85, pp. 8502-8505
(1988), and Klein et al BioTech vol. 24, pp. 384-386 (1992); each
of which is incorporated herein by reference).
One or more hydrogen oxide frozen particle vaccine compositions,
including, for example, one or more buffers, one or more immunogens
(e.g., viral protein subunits) and one or more adjuvants, as a
solution or suspension, are made by spraying the compositions
through an aperture or nozzle. Each vaccine composition is
propelled by a pressurized gas (e.g., compressed air) into a
compartment maintained at, for example, approximately -40.degree.
C.
The vaccine composition is delivered to at least one biological
tissue of a subject, for example, by propelling the particles via a
carrier gas under pressure (e.g., air, carbon dioxide, nitrogen)
through a tube directed toward at least one biological tissue
(including but not limited to plant callus, plant leaves, plant
roots, plant stems, vasculature, lymphatic, lymph node, epidermis,
subcutaneous, intramuscular, oral, nasal, pulmonary,
intraperitoneal or rectal tissue).
Alternatively, the vaccine composition is delivered to at least one
biological tissue of a subject, for example, by first forming the
frozen particle vaccine compositions through spraying composition
droplets into a cryogen bath (e.g., liquid nitrogen). The frozen
particle compositions are subsequently delivered to at least one
biological tissue by flash boiling liquid nitrogen, and propelling
the frozen particle compositions through a tube or barrel, for
example, to at least one biological tissue of a subject.
Frozen particle vaccine compositions containing one or more
reinforcement agents (e.g., silica beads) and of the appropriate
size and shape (e.g., bullet, spheroid, high aspect ratio shape)
penetrate the at least one biological tissue when propelled to high
velocity by a carrier gas. In one non-limiting example, a vaccine
composition approximately 20-70 .mu.m in size penetrates the
epidermis when the composition is accelerated to high speed with a
powder jet injector (PowerJect, PowerJect Pharmaceuticals) (Amorij
et al, Ibid.).
Similarly, one group found that using the Bio-Rad HELIOS Gene
Gun.RTM. and microparticle-delivery of pCMV-S DNA vaccination in
mice resulted in greater numbers of animals achieving immunity than
those receiving intramuscular injection.
For plant leaves, a high rate of infection with a Potyviridae virus
was obtained by another group using the Bio-Rad HELIOS Gene
Gun.RTM. and microparticle-delivery of the virus. The authors found
optimal infection rates in plant leaves under a helium pressure of
150 psi or 200 psi, at a distance of 0 cm from the delivery device
to the tissue. (Id. at page 2).
Example 11
Vaccine Compositions and Methods of Making Frozen Particles
Frozen particle vaccine compositions containing multiple
immunogens, for example, toxoids (chemically modified toxins) from
bacteria such as Clostridium tetani, Cornybacterium diphtheriae or
Bordetella pertussis, stimulate immunity to multiple bacteria or
toxins in a single vaccine composition.
Alternatively, multiple distinct immunogens, proteins, or peptides
that are derived from a single pathogen are combined in a single
frozen particle vaccine composition that immunizes a subject
against a pathogenic virus or bacteria that mutates frequently. For
example, multiple hemagglutinin or neuraminidase proteins, (e.g.,
H1N1, H3N2) from different viral strains (e.g., A/New
Calcdonia/H1N1, or A/Wellington/H3N2) or viral species of influenza
(e.g., influenza A or influenza B) are combined in a single frozen
particle vaccine composition and provides immunity to multiple
strains or species. (See e.g., Kamps et al, Influenza Report, pp.
127-149 (2006); world wide web at influenzareport.com/ir/vaccines;
each of which is incorporated herein by reference).
Alternatively, frozen particle vaccine compositions including one
or more immunogens, antigens or proteins (e.g., influenza A/New
Calcdonia/(H1N1)) are combined with one or more frozen particle
vaccine compositions containing one or more different antigens
(e.g., influenza B/Shanghai or influenza A/Wellington/(H3N2)). Such
a frozen particle vaccine composition combination provides immunity
against seasonal variants of viral pathogens.
In one non-limiting example, combinations of frozen particle
vaccine compositions including specific antigens from selected
influenza variants or strains target a seasonal flu epidemic.
(Kamps et al, Ibid.) Combination of frozen particle compositions
are made containing one or more different antigens or epitopes,
wherein the one or more different antigens or epitopes are derived
from mutant or variant HW proteins that evolve during HIV infection
(See e.g., Berzofsky et al, J. Clin. Inv. vol. 114, pp. 450-462
(2004)). Such combination compositions immunize a subject against
existing HIV mutants and anticipate the emergence of new HIV
mutants or variants.
Alternatively, one or more frozen particle vaccine compositions are
delivered to one or more mucosal tissues (e.g., nasal, oral,
rectal, pulmonary) via propulsion using a "pellet gun," via
inhalation, or ingestion by a subject. For example, an influenza
vaccine lyophilized and delivered nasally as spherical particles,
approximately 26.9 .mu.m (mean diameter), induces mucosal (e.g.,
nasal IgA response) and systemic immunity (e.g., serum antibody
response) to influenza virus (See e.g., Garmise et al, AAPS
PharmSciTech. vol. 8:E81 (2007); Huang et al, Vaccine. vol. 23(6),
pp. 794-801 (2004); each of which is incorporated herein by
reference).
Alternatively, the one or more frozen particle vaccine compositions
are delivered to one or more pulmonary surfaces of the subject via
propulsion by way of a "pellet gun," by using flash boiled liquid
nitrogen as a propellant, or by inhalation. Frozen particle
influenza vaccine compositions administered to one or more
pulmonary surfaces of a subject elicit mucosal and systemic
humoral, as well as cell-mediated immune responses to influenza
(See e.g., Amorij et al Vaccine. vol. 25, pp. 8707-8717 (2007),
which is incorporated herein by reference).
Example 12
Compositions and Methods of Making Frozen Particles
Frozen particle compositions of the appropriate size and shape,
including botulinum toxin, an optimal buffer (e.g., Hepes buffer),
one or more stabilizing agents, and one or more reinforcement
agents are administered through the skin of a subject to
neuromuscular junctions. Botulinum toxin inhibits acetylcholine
release, which blocks synapse formation, and temporarily paralyzes
the corresponding musculature.
Frozen particle compositions containing a recommended dose of
botulinum toxin (See e.g., Borodic, U.S. Pat. No. 5,183,462, which
is incorporated herein by reference), and at least one
reinforcement agent (e.g., polymer) are administered to skeletal
muscles using a delivery system derived from inkjet printer
technology that sprays picoliter quantities of the frozen particle
compositions at high velocity (e.g., 50 msec) toward the skin of
the subject. Botulinum toxin is typically administered by
subcutaneous injection (generally with a 26 gauge hypodermic
needle). Botulinum toxin is approved by the FDA for therapy of
strabismus (crossed-eyes), blepharospasm (uncontrolled blinking),
and other facial nerve disorders including hemifacial spasm. It is
also approved for treatment of cervical dystonia and glabellar
(frown) lines (See e.g., Jankovic, J. Neurol. Neurosurg. Psychiatry
vol. 75, pp. 951-957 (2004), which is incorporated herein by
reference).
In addition, botulinum toxin is included in the treatment of focal
or segmental dystonia (e.g., oromandibular-facial-lingual dystonia,
laryngeal dystonia, limb dystonia). Dystonias are neurological
disorders with repetitive and patterned contractions of muscles
that cause abnormal movements and postures. For example, cervical
dystonia subjects are injected with, for example, approximately 100
I.U of botulinum toxin, distributed over 3-5 injection sites,
spaced 5-15 mm apart, across the length of the sternomastoid
muscle. (Borodic, Ibid.)
Frozen particle compositions containing botulinum toxin are
administered to facial muscles that underlie frown lines, wrinkles,
and "crow's feet." For example, botulinum toxin is targeted to: 1)
the corrugator and procerus muscles to treat vertical glabellar
eyebrow furrows; 2) to multiple sites in the frontalis muscle to
eliminate horizontal lines in the forehead; or 3) to the lateral
orbicularis oculi to treat crow's feet.
Frozen particle compositions containing an optimal dose of
botulinum toxin (e.g., 0.2-0.4 I.U./kg) are administered over the
length of a specific facial muscle (e.g., orbicularis oculi) by use
of a delivery system with an inkjet nozzle. As described herein,
picoliter volumes of one or more frozen particle compositions are
sprayed at a velocity that achieves a desired or predetermined
depth (for example, 5-8 mm; Borodic, Ibid.). The velocity is also
altered according to the size, shape, and constituents of the
frozen particle composition.
Example 13
Methods of Administering Frozen Particle Therapeutic
Compositions
Frozen hydrogen oxide particles of ice Ic form and at least one
therapeutic agent or at least one diagnostic agent are formulated
for treatment of hematological cancers (e.g., leukemia or lymphoma)
or solid tumors (e.g., carcinoma, sarcoma). For example, at least
one of neo-adjuvant therapy, adjuvant therapy, chemotherapy,
antibody therapy, or immunotherapy are employed
In one non-limiting embodiment, frozen particle compositions are
used for adjuvant therapy of cancers treated with surgery such as
colon cancer, lung cancer, and breast cancer. At least one frozen
particle hydrogen oxide therapeutic composition containing one or
more reinforcement agents (e.g., silica beads, Kevlar.RTM.), one or
more buffers, one or more stabilizing agents (e.g., one or more
saccharides), and one or more cancer therapeutic agents (such as
one or more chemotherapy drugs, antibodies, biological agents
(e.g., antibodies, cytokines or peptides), or one or more
chemotherapeutic agents) are administered to an area proximal to a
region of at least one biological tissue where a tumor is present
or believed to be present. Optionally, resection of at least a part
of a tumor can be performed, with or without additional
administration of the at least one frozen particle therapeutic
composition.
The at least one frozen particle therapeutic composition is
administered in such a manner as described herein, that allows for
desired depth of penetration of the at least one biological tissue.
In one embodiment, the at least one frozen particle therapeutic
composition is administered to a depth that allows for at least one
of intracellular or intercellular delivery. For example, the at
least one frozen particle therapeutic composition is administered
to a depth that allows for delivery to at least one of epithelium,
endothelium, vasculature, lymphatic vessels, lymph nodes or
mucosa.
Specifically, if metastasis is present or believed to be present in
the subject, administration of the at least one frozen particle
therapeutic composition is delivered to such region of metastases
or micro-metastases are believed to be present.
Frozen particle hydrogen oxide therapeutic compositions provided as
an adjuvant therapy are administered by spraying at least one
composition under pressure with a carrier gas through a nozzle
designed to uniformly distribute particles over at least one
biological tissue at sufficient velocity to penetrate the tissue
exposed during tumor resection.
Advanced colon cancer (e.g., stage II, III) is treated surgically
by removal of sections of colon containing tumor with margins of
"normal" colon tissue and often includes removal of associated
lymph nodes and mesentery (colectomy). Standard adjuvant therapy
following surgery is systemic administration of a combination of
chemotherapy drugs (e.g., 5-fluorouracil, leucovorin or oxaliplatin
(FOLFOX)), (See e.g., Wolpin et al, CA Cancer J. Clin. vol. 57, pp.
168-185 (2007)). Systemic FOLFOX adjuvant therapy is associated
with significant toxicities including gastrointestinal toxicity,
neutropenia and neurotoxicity (Wolpin et al, Ibid.). Localized in
situ delivery of FOLFOX by administration of frozen particle
therapeutic compositions permits delivery of a lower dose.
Administration of at least one frozen particle hydrogen oxide
therapeutic composition containing at least one therapeutic
antibody includes, for example, bevacizumab (an anti-vascular
endothelial growth factor) or cetuximab (an anti-epidermal growth
factor receptor). Bevacizumab and cetuximab both target the
tumor-associated vasculature and tumor cells in the remaining colon
sections and the surrounding tissues, mesentery and lymph nodes.
Localized administration of therapeutic antibodies provides
sustained protection from recurrence of colon tumors at the site of
tumor resection and in the surrounding tissues. (Wolpin et al,
Ibid.). Following surgery and adjuvant therapy with one or more
frozen particle hydrogen oxide therapeutic compositions, including
at least one of one or more chemotherapy drugs, or one or more
antibodies, the remaining colon sections are spliced together (i.e.
anastomosis) or an artificial orifice (i.e. stoma) is inserted to
restore a functional colon.
Example 14
Methods of Administering Frozen Particle Therapeutic
Compositions
Frozen particle hydrogen oxide therapeutic compositions including
one or more cancer therapeutics or one or more cancer diagnostics
are used to treat cancers in distal locations from the primary
tumor or initial tumor site treated with surgery or radiation. For
example, colon cancer cells often metastasize to the liver ((Wolpin
et al, Ibid.). At the time of surgical resection of colon cancer
tumors, one or more frozen particle hydrogen oxide therapeutic
compositions including at least one cancer therapeutic, such as one
or more cytotoxic drugs (e.g., fluouracil), antibodies (e.g.,
cetuximab), radioisotopes conjugated to antibodies (e.g.,
.sup.131I-cetuximab), or one or more mixtures of at least one
cytotoxic drug and at least one biological-based therapeutic agent
are administered to the liver and surrounding tissues.
Administration of the at least one frozen particle hydrogen oxide
therapeutic composition is accomplished by traditional surgery or
laparoscopic surgery that allows access to the liver (or other
organs to be treated). Administration of at least one frozen
particle hydrogen oxide therapeutic composition directly to the
liver and the surrounding vasculature allows for intracellular or
intercellular penetration and release of at least one anti-cancer
therapeutic for treatment of any existing or suspected colon cancer
mestastases or micro-metastases.
As described herein, the at least one frozen particle hydrogen
oxide therapeutic composition including one or more cancer
therapeutics are administered by way of a spraying device. Such a
spraying device includes an insulated tube and nozzle, as well as a
valve that controls the flow of particles. In the case of
traditional surgery for tumor or tissue resection, the at least one
frozen particle hydrogen oxide therapeutic composition is sprayed
directly onto the target tissue or tissues. Whereas in the case of
laparoscopic surgery for tumor or tissue resection, the at least
one frozen particle hydrogen oxide therapeutic composition is
sprayed through a trocar (a hollow tube approximately 10
millimeters in diameter).
In certain spraying devices, the at least one frozen particle
hydrogen oxide therapeutic composition is administered by way of a
carrier gas. The depth of penetration by the at least one
therapeutic composition is controlled by regulating the carrier gas
pressure as well as the consequent particle velocity. The at least
one therapeutic composition optionally includes one or more tracer
agents or is delivered simultaneously with one or more tracer
agents. Some non-limiting examples of tracer agents include dyes,
stains or fluorescent compounds that mark the tissue area sprayed.
The one or more tracer agents can optionally monitor or provide
feedback as to the quantity or quality (in the case of multiple
therapeutic compositions administered simultaneously or over time)
of the at least one therapeutic composition administered to a
specific site.
In one embodiment, the at least one frozen particle hydrogen oxide
therapeutic composition including at least one cancer therapeutic
further includes hematoxylin and eosin stains mixed at a known
ratio (e.g., 1:10). Alternatively, a batch of the at least one
frozen particle hydrogen oxide therapeutic composition is
administered in a mixture or in separate applications frozen
particles including hematoxylin and eosin stains. Staining of
tissues is visualized by inspection with a low power microscope
(e.g., dissection microscope) or with a laparoscope, which allows
for assessment of the relative quantity or quality of the at least
one therapeutic composition administered to the tissue. Staining of
the tissues further provides a guide as to the region that received
the at least one therapeutic composition.
Example 15
Methods of Administering Frozen Particle Therapeutic
Compositions
Frozen particle hydrogen oxide therapeutic compositions including
carbon dioxide and at least one cancer therapeutic are administered
to at least one tumor or tissue suspected of being cancerous. Upon
administration, the frozen particle hydrogen oxide therapeutic
compositions penetrate one or more tumor cells, warm to ambient
temperature, and undergo rapid sublimation and gaseous expansion of
the carbon dioxide. This rapid reaction produces a small explosion
that destroys at least one tumor cell as well as one or more
adjacent cells. In addition, administration of the frozen particle
therapeutic compositions at low temperatures (e.g., lower than
approximately -78.5.degree. C., which is the approximate
sublimation temperature for carbon dioxide at 1 atm pressure),
freezes cells and tissues, causing tumor cell death (See e.g.,
Vergnon et al, Eur. Respir. J. vol. 28 pp. 200-218 (2006);
incorporated herein by reference).
Alternatively, carbon dioxide gas is entrapped in frozen particles
by placing the liquid phase (e.g., hydrogen oxide) under high
pressure in the presence of carbon dioxide gas. (See e.g., U.S.
Pat. Nos. 4,289,794; 4,289,790; 4,262,029; 5,439,698, each of which
is incorporated herein by reference). Administration of the at
least one therapeutic composition is conducted as described herein.
In one embodiment, the use of a tube and nozzle is used that sprays
the frozen particle therapeutic compositions under pressure in a
carrier gas (e.g., carbon dioxide, nitrogen). Administration of the
at least one therapeutic composition is carried out as an adjuvant
therapy in conjunction with tumor resection, or as an alternative
when tumor resection is not favored. For example lung cancer tumors
are generally inoperable when such tumors are adjacent to airways,
or infiltrate central airways including the trachea, main stem
bronchi or multiple lung lobes. Additionally, subjects with
compromised respiration (e.g., those with lung disease, heart
disease or advanced age) are generally not candidates for surgery
(See e.g., Spiro et al, Amer. J. Respir. Crit. Care Med., vol. 172,
pp. 523-529 (2005); which is incorporated herein by reference).
Carbon dioxide frozen particle therapeutic compositions including
one or more chemotherapeutic drugs (e.g., cisplatin, docetaxel,
vinorelbine), targeted drugs (e.g., gefitnib, erlotnib), or
biological-based agents (e.g., cetuximab, panitumumab, bevacizumab)
are administered directly onto lung cancer tumors. Administration
is conducted via endoluminal bronchoscopy or by video-assisted
thoracoscopy by means of an insulated tube and nozzle integral to
the endoscopic device. Frozen particle composition velocities and
spray rate are controlled by a valve between the spray head and the
compartment of the "pelletizer." (See e.g., U.S. Pat. Nos.
6,306,119, or 6,764,493, each of which is incorporated herein by
reference). Precise localization and administration of the frozen
particle therapeutic compositions are accomplished by bronchoscopy
and endoscopy with fluoroscopy used to mark the field(s) of
interest.
Methods for endoscopic targeting of tumors are described, for
example, in Huber et al (Chest vol. 107, pp. 463-470 (1995); which
is incorporated herein by reference). Moreover, computed
tomography, magnetic resonance imaging, positron emission
tomography or other techniques are used to locate lung cancer
tumors.
Frozen particle therapeutic composition administration by using
endoscopic procedures or as an adjuvant therapy in conjunction with
traditional surgery is used for various regions of existing or
potential carcinogenesis, including mediastinal lymph nodes,
vasculature, chest wall and other thoracic sites.
Alternatively, frozen particle therapeutic compositions are
delivered during traditional surgery for lung cancer and used to
treat inoperable tumors remaining following lobectomy, wedge
resection, and pneumonectomy, as well as to treat margins of lobe,
wedge or lung excisions to reduce recurrence of lung cancer.
Without wishing to be bound by any particular theory, frozen
particle carbon dioxide therapeutic compositions maintained at
approximately -80.degree. C. while administered to tumors rapidly
freeze the tumor cells leading to formation of ice crystals in
tumor cells that destroy cell organelles (e.g., mitochondria)
leading to death of the tumor cells. (Vergnon et al, Ibid.)
Similarly, frozen particle therapeutic compositions containing at
least one radioactive element deliver radiation to lung cancer
tumor cells. One non-limiting example utilizes frozen particle
therapeutic compositions including .sup.192Iridium for irradiating
lung tumors that obstruct major airways. Administration of the
frozen particle therapeutic compositions is conducted using an
endoscope and a wire to place the radioactive compositions in at
least one lung tumor. Without wishing to be bound to any theory,
tumor cell irradiation results in single-stranded DNA breaks that
induce apoptosis and reduce rates of cell division (Vergnon et,
Ibid.).
Example 16
Compartmentalized Frozen Particle Therapeutic Compositions
Frozen particles formed in a bullet-shaped mold with hollow cores
or cavities that can be filled with therapeutics are useful for
delivering at least one therapeutic agent to a variety of specific
tissues, cells and organ or body locations. Hollow bullet-shaped
frozen particles can be filled with a therapeutic agent such as one
or more of an antibody, cytokine, DNA, small interfering RNA,
microRNA, aptamer, cytotoxic agent (e.g. a xenobiotic, synthetic,
or radioactive agent) that are in aqueous solution (e.g. sodium
phosphate buffer) or form a suspension. Alternatively, hollow
frozen bullets can be filled with one or more liquid or solid
polymers or nanoparticles that contain at least one therapeutic
agent (e.g. at least one prodrug) that requires activation.
In one particular embodiment, at least one therapeutic agent is
frozen in carbon dioxide. The frozen carbon dioxide/therapeutic
agent mixture or solution is used to fill pre-formed hollow
bullet-shaped frozen particles. In certain embodiments, the hollow
bullet-shaped frozen particles are formed and filled
simultaneously. The temperature and pressure of the frozen
particles are adjusted according to the particular constituents and
specific parameters of the desired frozen particle.
Administration of at least one compartmentalized therapeutic frozen
particle composition with a spraying device allows for localized
delivery of at least one therapeutic agent to specific cells or
tissues, such as one or more tumors. In certain embodiments,
administration of at least one compartmentalized therapeutic frozen
particle composition is directed to one or more adjacent,
metastatic, or affected tissues including lymph nodes, lymphatic
vessels, blood vessels, and organs (e.g. liver, lung, and
kidney).
The size, shape or delivery velocity of the at least one
compartmentalized frozen particle composition can be controlled in
order to deliver the at least one particle composition to a desired
location or penetration depth. In certain embodiments, the
compartmentalized frozen particle composition includes at least one
therapeutic agent (e.g. a cytotoxic agent) that is delivered
intracellularly, intercellularly, or into the lumen of vasculature,
lymphatics, alveoli, bladder, intestine, lungs or into a specific
tissue (e.g. endoderm, smooth muscle, skeletal muscle,
prostate).
In one example, hollow bullet-shaped frozen particle compositions
containing a prodrug, such as capecitabine, can be delivered
intracellularly to tumor cells (e.g. colon carcinoma) where
capecitabine is metabolized to 5-fluorouracil, an active cytotoxic
agent. Administration of at least one frozen particle composition
including capecitabine specifically to tumor cells and optionally
to proximal tissues allows for the potential to increase the
therapeutic dose to tumor cells, while reducing systemic exposure
(which can lead to toxicity and side effects, including angina and
myocardial infarction, diarrhea, nausea, neutropenia, anemia and
thrombocytopenia).
Alternatively, in one embodiment, intracellular delivery of at
least one frozen particle composition including capecitabine that
is encapsulated in biodegradable polymeric nanoparticles, releases
capecitabine in a pH-dependent manner. (See for example, Shenoy et
al, Pharm. Res. vol. 22, pp. 2107-2114 (2005), which is
incorporated herein by reference). Since tumor cells generally have
a lower pH than non-tumor cells, the capecitabine is released in
higher amounts in the tumor environment.
Alternatively, in one embodiment, at least one frozen particle
includes capecitabine and one or more polymeric nanoparticles
composed of at least poly(.di-elect cons.-caplactone) (PCL), a
non-pH sensitive polymer that is able to release capecitabine as
the frozen particle melts or sublimates. (See, for example, Shenoy
et al, Ibid.).
Example 17
Compartmentalized Frozen Particle Therapeutic Compositions
Including Reinforcement Agents for Transdermal Administration
Frozen particle compositions that include at least one therapeutic
agent in one or more distinct regions of the particles are useful
for transdermal administration of at least one therapeutic to
various layers of the skin or to underlying tissues, organs and
structures. For example, treatment of certain skin disorders, such
as psoriasis, is currently limited to topical administration of a
therapeutic agent (e.g. coal tar, corticosteroids, vitamin D.sub.3
analogs, or retinoids), systemic treatments (e.g. methotrexate,
cyclosporin and retinoids), or UV irradiation (e.g. phototherapy)
(See, for example, en.wikipedia/wiki/psoriasis2008, which is
incorporated herein by reference). None of these current treatments
are fully effective.
In one embodiment, at least one frozen particle composition
including one or more psoriasis therapeutic agents located in one
or more gradation layers of concentration, or as a coating on the
particle is administered to the epidermis, dermis or hypodermis
layer by controlling specific parameters, such as particle
hardness, size, shape, reinforcement agent, or velocity. For
example, frozen particle compositions including reinforced hydrogen
oxide are propelled toward at least one biological tissue by
"flash-boiling" liquid nitrogen to create nitrogen gas and propel
the particle compositions by explosive force. The frozen particle
compositions are reinforced with plant matter (such as silk fibers,
or collagen fibers), or spun metallic fibers (such as tungsten,
iron, manganese, carbon, titanium, or steel). The one or more
frozen particle compositions are directed with a hose and nozzle
device onto psoriatic skin. In addition, the frozen therapeutic
particle compositions can be delivered to the dermis to further
impact any pathogenic T cells or cytokines associated with the
condition.
In one embodiment, hollow bullet-shaped frozen particle
compositions containing one or more biological agent, for example
etanercept (as an anti-TNF-.alpha. therapy), are administered to
the dermal layer underlying areas of psoriatic skin. One or more
other therapeutic agents can be combined with the one or more
biological agent on the same frozen particle, or on different
frozen particles for administration. For example, cytotoxic or
cytostatic agents are administered to cells associated with
psoriasis, including T1 cells, T.sub.H17 cells, dendritic cells,
neutrophils or keratinocytes. (See, for example, Sabat et al, Exp.
Derm. vol. 16, pp. 779-798 (2007), which is incorporated herein by
reference). For example, therapeutic agents such as anti-CD3,
anti-IL-23, anti-IL-17 or cyclosporin are included in one or more
frozen particles to further treat psoriasis in the dermis or
epidermis.
Example 18
Compartmentalized Frozen Particle Therapeutic Compositions
Including Explosive Materials
Hollow frozen particle compositions including one or more
reinforcement agents and hydrogen oxide are filled with solid
carbon dioxide. The hollow frozen particle compositions are useful
for destroying, debriding, ablating, or eliminating unwanted cells
or tissues such as fat, bone or tumor cells. In one embodiment, the
hollow frozen particle compositions containing a solid carbon
dioxide core produces an explosive force as the particle sublimates
or melts during administration of the frozen particle compositions.
The explosive force fragments, abrades, or destroys cells or
tissues.
At least one sub-group of the frozen particle composition treatment
course includes one or more of an antibiotic or other
anti-microbial agent; one or more anti-inflammatory drugs; one or
more anesthetics or analgesics; or one or more vasoconstrictors.
Targeted delivery of hollow frozen particle compositions to
unwanted cells or tissues is regulated by controlling, for example,
frozen particle hardness, size, shape, reinforcement agents or
explosive agents, and velocity. One or more frozen particle
compositions are administered to at least one biological tissue by
external (e.g. transdermal) methods, or internal (e.g.
laparoscopic) methods. In one embodiment, a device (e.g. tube and
spray nozzle) is integrated for administration of the one or more
frozen particle compositions.
Compartmentalized frozen particle compositions are useful for
destroying adipocytes or fatty tissue. Present treatments include
liposuction, which is performed with a cannula attached to an
aspirator that is inserted through small incisions proximal to
unwanted fat and the cannula are drawn over the fat to dislodge it
and aspirate it.
In one embodiment, a tube and spray nozzle is integrated with the
cannula for administration of frozen particles containing a solid
carbon dioxide core and optionally, one or more therapeutic agents.
For example, the operator sprays frozen particle compositions
containing carbon dioxide toward the adipocytes or fatty tissue in
order to remove or destroy the tissue. Next, the treated tissue is
aspirated with the cannula.
In one embodiment, a laparoscope can be used with the delivery
device to allow visualization of the fatty tissue as well as
precise delivery of the one or more frozen particle compositions.
In certain embodiments, the frozen particle compositions also
include lidocaine or ibuprofen in order to minimize pain and
inflammation often associated with liposuction. In certain
embodiments, at least one vasoconstrictor, such as epinephrine, is
included in the one or more frozen particles in order to minimize
bleeding. In certain embodiments, antibiotics, such as penicillin
or sulfonamide, are included to reduce infection.
Alternatively, frozen particle compositions including a solid
carbon dioxide core, one or more antibiotics, analgesics,
anti-inflammatory drugs or vasoconstrictors are delivered
transdermally to adipose tissue by spraying the particle
compositions as described herein, at the appropriate velocity to
penetrate the epidermis, dermis or hypodermis. Following treatment
of adipocytes or fatty tissue with the one or more frozen
particles, liposuction is performed to remove the treated cells or
tissues. In one embodiment, adipocytes are selectively treated with
minimal effect on the underlying muscle cells, which reduces
bruising or bleeding.
Example 19
Compositions and Methods of Administering Frozen Particles
Including One or More Adhesive Agents and One or More Biological
Remodeling Agents
Frozen particles including hydrogen oxide, carbon dioxide,
dimethylsulfoxide or a buffer (e.g. HEPES, Ringer's solution,
sodium citrate, sodium phosphate, etc.) are formulated with at
least one adhesive agent such as cyanoacrylate, polyethylene glycol
polymers or albumin plus glutaraldehyde.
Frozen particle compositions including at least one adhesive agent
are utilized in conjunction with standard methods to achieve
hemostasis in patients undergoing surgery, for example, to repair
large blood vessels such as the aorta, femoral or carotid arteries.
Frozen particle compositions including bovine albumin and
glutaraldehyde (BIOGLUE.RTM., CryoLife, Inc., Kennesaw, Ga.) are
utilized, for example, in repair of an aortic dissection or other
blood vessel repair.
Frozen particle compositions including hydrogen oxide,
glutaraldehyde, and bovine albumin are produced as described herein
at other sections. In an embodiment, various different subsets of
frozen particle compositions are produced, for example, one subset
includes frozen hydrogen oxide particles including glutaraldehyde,
while another subset is produced that includes frozen hydrogen
oxide particles including bovine albumin.
In an embodiment, a single set of frozen particle compositions are
produced, for example, including frozen hydrogen oxide particles
including both glutaraldehyde and bovine albumin.
In an embodiment, a set of frozen particle compositions are
produced, for example, that includes compartmentalized particles
wherein both glutaraldehyde and bovine albumin are present on a
particular particle, but each is partially or wholly sequestered in
a separate compartment of the particular particle. Some examples of
compartmentalized frozen particles are described herein at other
sections.
In an embodiment, frozen particles include bovine albumin in a mass
ratio of weight per volume of approximately 5%, approximately 10%,
approximately 15%, approximately 20%, approximately 25%,
approximately 30%, approximately 35%, approximately 40%,
approximately 45%, approximately 50%, approximately 55%,
approximately 60%, approximately 65%, approximately 70%,
approximately 75%, or any value therebetween.
In an embodiment, frozen particles include glutaraldehyde in a mass
ratio of weight per volume of approximately 1%, approximately 2%,
approximately 3%, approximately 4%, approximately 5%, approximately
6%, approximately 7%, approximately 8%, approximately 9%,
approximately 10%, approximately 11%, approximately 12%,
approximately 15%, approximately 16%, approximately 17%,
approximately 18%, approximately 19%, approximately 20%, or any
value therebetween.
One or more sets of frozen particle compositions including hydrogen
oxide, glutaraldehyde, and/or bovine albumin, as described herein,
are administered to the false lumen of the dissected aorta or other
blood vessel in need of repair, at the distal and proximal
anastomotic sites.
In an embodiment, a set of frozen particle compositions including
bovine albumin and glutaraldehyde is administered alone or in
conjunction with (sequentially or simultaneously with) other frozen
particle compositions that optionally include, for example, one or
more of at least one therapeutic agent, at least one reinforcement
agent, at least one explosive material.
In an embodiment, multiple sets of frozen particle compositions,
including bovine albumin and glutaraldehyde on separate particles
are administered simultaneously or sequentially to the biological
tissue. These multiple sets of frozen particle compositions are
optionally administered simultaneously or sequentially with other
frozen particle compositions that include, for example, one or more
of at least one therapeutic agent, at least one reinforcement
agent, or at least one explosive material.
Depending on the thickness of the blood vessel to be repaired, as
well as other factors, an adhesive layer is administered with a
thickness of approximately 0.1 mm, approximately 0.2 mm,
approximately 0.3 mm, approximately 0.4 mm, approximately 0.5 mm,
approximately 0.6 mm, approximately 0.7 mm, approximately 0.8 mm,
approximately 0.9 mm, approximately 1.0 mm, approximately 1.5 mm,
approximately 2.0 mm, approximately 2.5 mm, approximately 3.0 mm,
approximately 3.5 mm, approximately 4.0 mm, approximately 4.5 mm,
approximately 5.0 mm, approximately 6.0 mm.
Optionally, subsequent to repair of the distal and proximal ends of
the blood vessel, one or more support structural materials are
inserted to replace damaged blood vessel sections. Some examples of
structural material that can be utilized are described herein at
other sections. For example, some non-limiting examples of
structural material include one or more of tubing (such as plastic
or rubber tubing, e.g. polyethylene terephthalate or
polytetrafluoroethylene), a stent (optionally including one or more
therapeutic agents), a matrix (such as extracellular matrix
components, or an artificial or synthetic matrix), a rod or other
physical support.
Following insertion of the optional support structure, one or more
sets of frozen particle compositions are administered to the
repaired blood vessel to secure the structure or assist in
modulating hemostasis. One or more sets of frozen particle
compositions are also optionally administered to the junctions
between the support structure and the vasculature.
Example 20
Compositions and Methods of Administering Frozen Particles
Including One or More Adhesive Agents and One or More Biological
Remodeling Agents
Surgical incisions, burns, and other traumatic injuries result in
damage to the dermis or hypodermis skin layers. Frozen particles
including at least one adhesive agent, and optionally one or more
of a growth factor, an anesthetic, or an antibiotic are
administered to the biological tissue to secure would closure,
including securing skin grafts. The frozen particles are
administered alone or in conjunction with surgical staples or
sutures.
In an embodiment, one or more frozen particles including thrombin
(e.g., activated thrombin) or fibrinogen are administered. As
described in other sections herein, thrombin and fibrinogen can be
included as part of a single frozen particle (including, for
example, provided in compartments of a single frozen particle), a
single set of frozen particles, or separately as part of different
frozen particles or different sets of frozen particles. As
described herein, if multiple sets of frozen particles are
administered, the sets can be administered simultaneously or
sequentially.
In an embodiment, one or more frozen particles including at least
one adhesive agent include a biodegradable polymer that
encapsulates at least one therapeutic agent (such as a growth
factor, antibiotic, anesthetic or other agent). For example,
poly(.di-elect cons.-caprolactone) (PCL) allows for controlled or
sustained release of a therapeutic agent for a specific location
(See, for example, Shenoy et al, Ibid., which is incorporated
herein by reference).
In an embodiment, one or more frozen particles include activated
thrombin at a concentration of approximately 0.5 IU/mL,
approximately 1.0 IU/mL, approximately 1.5 IU/mL, approximately 2.0
IU/mL, approximately 2.5 IU/mL, approximately 3.0 IU/mL,
approximately 3.5 IU/mL, approximately 4.0 IU/mL, approximately 4.5
IU/mL, approximately 5.0 IU/mL, approximately 5.5 IU/mL,
approximately 6.0 IU/mL, approximately 6.5 IU/mL, approximately 7.0
IU/mL, approximately 7.5 IU/mL, approximately 8.0 IU/mL,
approximately 8.5 IU/mL, approximately 9.0 IU/mL, or any value
therebetween.
In an embodiment, one or more frozen particles include fibrinogen
at a concentration of approximately 20 mg/mL, 30 mg/mL, 40 mg/mL,
50 mg/mL, 60 mg/mL, 70 mg/mL, 80 mg/mL, 90 mg/mL, 100 mg/mL, 110
mg/mL, 115 mg/mL, 120 mg/mL, 130 mg/mL, 140 mg/mL, 150 mg/mL, or
any value therebetween.
Since activated thrombin reacts with fibrinogen by way of
proteolysis to form a fibrin adhesive, the concentration of either
fibrinogen or thrombin can be increased or decreased, depending on
the desired goal of wound closure. (See, e.g., Spotnitz et al.
Transfusion, vol. 48, pp. 1502-1516 (2008); Evans et al., Braz. J.
Urol. vol. 32, pp. 131-141 (2006), each of which is incorporated
herein by reference.) For example, if a skin graft is involved in
the wound repair and a slow rate of adherence is desired in order
to accurately place the graft on the wound, the concentration of
either thrombin or fibrinogen can be reduced. Alternatively,
separate sets of one or more frozen particles can be administered,
wherein the concentration of at least one adhesive agent varies
within a set or between the separate sets of frozen particles.
Optionally, one or more frozen particles can include at least one
proteolytic inhibitor, such as aprotinin, in order to prolong the
fibrin adhesive effect. (See, e.g., Spotnitz et al, Ibid., which is
herein incorporated by reference).
Optionally, one or more of the frozen particles includes at least
one detection material (e.g., a non-reactive, biodegradable dye or
non-toxic contrast agent) that allows for visual detection of
application of the one or more frozen particles. In an embodiment,
the one or more frozen particles including at least one detection
material also include at least one other agent (e.g., at least one
adhesive agent, or at least one therapeutic agent). (See, e.g.,
worldwide web at kolorjectchemicals.com/natural-food-color.html,
visited on Nov. 25, 2008, which is incorporated herein by
reference.)
Optionally, frozen particles are administered that include one or
more growth factor (e.g., keratinocyte growth factor, vascular
endothelial growth factor A, epidermal growth factor, fibroblast
growth factor, or hepatocyte growth factor) to promote engraftment.
(See, for example, Nolte et al, Cells Tissue Organs, vol. 187, pp.
165-176 (2008); Boateng et al., J. Pharm. Sci. vol. 97, pp.
2892-2923 (2008), each of which is incorporated herein by
reference). In addition or instead of these growth factors, one or
more frozen particles include one or more of collagen, hyaluronic
acid, glycosaminoglycans, or other extracellular matrix components,
at least one of which is encapsulated in a PCL polymer. (See, for
example, Boateng et al., Ibid, which is incorporated herein by
reference.)
In an embodiment, compartmentalized frozen particles including one
or more of activated thrombin, fibrinogen, antibiotic (e.g.,
minocycline, gentamycin, oxoflacin, or tetracycline), or
PCL-encapsulated extracellular matrix or growth factor are
administered to a wound.
In an embodiment, one or more frozen particles include one or more
cells (e.g., pluripotent stem cells, mesenchymal stem cells,
fibroblasts, keratinocytes, dermal progenitor cells) to assist in
wound repair, including skin engraftment. For example, dermal
fibroblasts suspended in cryogenic media (e.g., containing 10%
dimethylsulfoxide) are included in one or more frozen particles. In
the same or different frozen particle, one or more of at least one
growth factor, at least one extracellular matrix component, or at
least one adhesive agent are included. Optionally, one or more of
the agents included in the frozen particles are encapsulated by PCL
or another polymer. The frozen particles can be administered
simultaneously or sequentially.
In an embodiment, several different sets of frozen particles are
administered in order to establish layers of, for example,
extracellular matrix, fibroblasts, fibrin sealant, and
keratinocytes can be administered in multiple layers with or
without an additional skin graft. In an embodiment, the skin graft
itself has been derived artificially or synthetically, at least in
part, by administration of frozen particles including various skin
components to at least one biological tissue or a synthetic matrix
(e.g., biodegradable sponge or polymer matrix).
Optionally, as in the case of burns or other wounds in which
necrotic tissue is present, frozen particles are administered to
debride tissue prior to would closure or skin engraftment. Frozen
particles including one or more of at least one antibiotic (e.g.,
neomycin, polymixin B, or gramicidin), or at least one anesthetic
(e.g., lidocaine). As described herein at other sections,
debridement of cells or tissue is regulated by several factors,
including characteristics of the one or more frozen particles
(e.g., size, shape, or constitution of any particular frozen
particle), as well as characteristics of administration of the one
or more frozen particles (e.g., velocity of delivery, angle of
delivery, quantity of particles delivered, or rate of
delivery).
In an embodiment in which tissue is debrided, a device is utilized
to administer the one or more frozen particles, as described herein
at other sections. In an embodiment, a tube and nozzle is utilized
to administer the one or more frozen particles, with an optional
aspirator tube to remove liquid and tissue as debridement
occurs.
Example 21
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Remodeling Agents, One or More
Therapeutic Agents, One or More Adhesive Agents, and One or More
Reinforcement Agents for Tissue Reconstruction
Frozen particle compositions including one or more of a
reinforcement agent, antibiotic, therapeutic agent, polymer,
adhesive, stem cell, or progenitor cell are utilized for debriding
damaged or necrotic tissue, such as bone and cartilage.
Subsequently, one or more frozen particle compositions as described
are utilized for reconstructing the tissue, in addition to or
instead of one or more frozen particle compositions including one
or more of a growth factor, progenitor cell or stem cell.
For example, joint restructuring or replacement is a common
surgical procedure for joints such as knee or hip joints. Knee
replacement surgery is performed as a partial or total knee joint
replacement. Standard knee replacement generally includes replacing
or supplementing diseased or damaged joint surfaces with bone
grafts (e.g., autologous or cadaveric bone grafts) or synthetic
materials (e.g., metal, plastic, or rubber substrates).
Optionally, computer systems are used to model the bone defect,
based on imaging studies (e.g., x-ray, computed tomography (CT), or
other imaging). Among other things, imaging the bone or other
tissue (e.g., cartilage), allows for assessment of the defect, or
analysis of the present joint structure, allows for assistance in
designing repair or replacement of the joint, and provides guidance
for delivery of the frozen particle compositions. In certain
instances, the frozen particle compositions are delivered by way of
a piezoelectric or inkjet printer device that is directly or
indirectly under the control of a computer system.
In an embodiment, a CT scan is used to develop a three-dimensional
image of the joint to be reconstructed. For a knee joint, for
example, regions from the distal femur and proximal tibia,
including synovial and cartilage, can be imaged for assessment.
Computer systems and methods for designing and repairing the
joint(s) can also be used for comparing the present state of the
subject's joint with that of a healthy individual. Thus, the repair
may include reconstructing or restructuring the joint according to
healthy or undamaged joints.
Optionally, a computer system also controls a robotic arm or other
automated instrument containing a piezoelectric or inkjet printer
device, or sprayer for administration of one or more frozen
particle compositions in the reconstruction of the joint. In
certain instances, the subject's damaged or diseased joint is
ablated or debrided with one or more frozen particle compositions
in addition to or instead of reconstructing the joint. In certain
instances, one or more frozen particles are delivered to a
substrate (e.g., natural, artificial, or synthetic materials) used
in reconstructing the subject's knee joint. In certain instances,
the substrate includes an artificial knee joint or a cadaveric knee
joint.
In the case where the subject's joint is ablated or debrided, one
or more frozen particle compositions are administered to the
subject's joint (optionally with assistance of a computer system).
The ablation or debridement may be performed before, during, or
subsequent to the administration of one or more frozen particle
compositions related to stabilizing the joint or reconstructing the
joint. For example, frozen particle compositions including
reinforcement agents (e.g., silica beads, fiberglass, polyethylene
glycol) are propelled toward the subject's knee joint at or to a
predetermined velocity that allows for delivery of the compositions
into the various layers of the joint (i.e., skin, subcutaneous
layers, synovial membrane, etc.).
In an embodiment, an arthroscopic device is utilized for delivery
of one or more frozen particle compositions to the knee joint. A
computer system can assist a surgeon in ablating or debriding the
cartilage and/or bone to the proper depth by delivering the frozen
particle compositions at a predetermined or preselected set of
parameters. The predetermined or preselected parameters include,
but are not limited to, size of frozen particle compositions, shape
of frozen particle compositions, constitution of frozen particle
compositions, velocity at which frozen particle compositions are
delivered, angle at which frozen particle compositions are
delivered, timing for delivery of specific frozen particle
compositions, or programs for cycling any one or more parameters.
In an embodiment, ablation is performed on a knee joint with
guidance provided by a computer system or imaging apparatus. During
or subsequent to ablation, frozen particle compositions containing
therapeutic agents (such as at least one antibiotic or
anti-inflammatory agent) are administered to the joint.
In an embodiment, the joint is reconstructed by utilizing a
computer system for imagine or modeling the joint. Optionally, the
computer system is directly or indirectly linked to a sprayer or
piezoelectric or inkjet printer device capable of administering one
or more frozen particle compositions. In certain instances, the
frozen particle compositions administered to reconstruct the joint
include scaffolding materials of natural, artificial, or synthetic
origin (examples of specific agents include, but are not limited
to, antibodies; growth factors; e.g., bone morphogenic protein;
polymers; e.g., polylactic acid, polylactic acid-co-glycolic acid;
or adhesives; e.g., polyethylmethacrylate/tetrahydrofurfuryl
methacrylate, hydroxyapatite, etc.), or an amphiphilic polymer. In
one embodiment, the delivery of one or more adhesive agents or at
least one biological remodeling agents, includes at least one
temporally-regulated method. (See, e.g., Davies, et al. Advanced
Drug Delivery Reviews, vol. 60, pp. 373-387 (2008); or Kanczler et
al. Biomaterials, vol. 29, pp. 1892-1900 (2008), each of which is
incorporated herein by reference.)
In an embodiment, scaffolding materials solidify in situ at
physiological temperature and pH, and may include, but not be
limited to, calcium phosphate cement with a biocompatible gelling
agent and scaffold materials for cartilage regeneration (e.g.,
oligopoly-ethylene glycol fumarate,
polyN-isopropylacrylamideco-acrylic acid,
polyN-isopropylacrylamide-grafted gelatin, polyethylene oxide,
alginate, fibrin, PLGA-g-PEG, pluronics, calcium
phosphate/hyaluronic acid composites, hyaluronic acid gel and
chitosan. See, e.g., Hou et al., J. Mat. Chem. vol. 14, pp.
1915-1923 (2004), which is incorporated by reference herein.
Optionally, one or more frozen particle compositions including
scaffolding materials that promote adhesion of cell types that
produce bone or cartilage are administered to assist in
reconstructing the subject's joint. For example, integrin peptides
with the arginine-glycine-aspartic acid (RGD) sequence can be
covalently coupled with other scaffolding materials administered to
the joint. Integrins are capable of promoting adhesion of cells,
including osteoblasts, via their integrin receptors. See, e.g.,
Hou, et al., Ibid.
Optionally, one or more frozen particle compositions including
antibodies or antibody fragments are chemically coupled with
scaffold polymers that among other things, promote binding and
retention of specific cell types within the scaffold, are
administered to the subject's knee or a substrate used in
reconstructing the knee. For example, anti-integrin
.alpha..sub.V.beta..sub.3 antibodies recognize endothelial cells,
and anti-integrin .alpha..sub.5 antibodies recognize chondrocytes,
both of which cell types can assist in reconstructing the joint.
See, e.g., Hou et al, Ibid.
Optionally, one or more frozen particle compositions including one
or more growth factors that are capable, for example, of promoting
cell growth and/or cell differentiation are administered in
reconstructing the knee joint. For example, bone morphogenic
proteins, fibroblast growth factors, vascular endothelial growth
factors, or other factors are encapsulated in polymer particles
(e.g., vesicles) that form at least part of a scaffold to support
reconstruction of the joint. See, e.g., Davies et al., Ibid. In an
embodiment, one or more growth factors support the infiltration or
growth of osteocytes, chondrocytes, or vascular cells.
In an embodiment, one or more frozen particle compositions
including one or more of a progenitor cell, stem cell, osteoblast,
chondrocyte, or endothelial cell are administered. In an
embodiment, one or more subsets of frozen particle compositions
include, but are not limited to compositions containing one or more
of a scaffolding material, adhesive agent, or growth factor. In an
embodiment, one or more subsets of frozen particle compositions are
administered to the subject's joint simultaneously, sequentially,
or cyclically.
In an embodiment, reconstruction of the joint is conducted by
administering one or more subsets of frozen particle compositions
through interaction or consultation with a computer system. In an
embodiment, administration of one or more frozen particle
compositions or one or more subsets of frozen particle compositions
occurs in a stepwise fashion according to one or more parameters
including, but not limited to, size of frozen particle
compositions, shape of frozen particle compositions, constitution
of frozen particle compositions, velocity at which frozen particle
compositions are delivered, angle at which frozen particle
compositions are delivered, timing for delivery of specific frozen
particle compositions, or programs for cycling any one or more
parameters.
In an embodiment, the joint is debrided, and the surface is
prepared for reconstruction. Additionally, one or more frozen
particle compositions or one or more subsets of frozen particle
compositions are administered containing one or more of a
scaffolding material, an adhesive agent, a therapeutic agent, a
reinforcement agent, or an explosive agent. For example, calcium
phosphate cement with a biocompatible gelling agent are included
with one or more frozen particle compositions. In the same or
different frozen particle compositions, growth factors (such as
vascular endothelial growth factors or bone morphogenic factors)
are included. In addition, in the same or different frozen particle
compositions, osteoblast cells or osteoblast precursor cells are
administered to the subject's joint or a substrate used for
reconstructing the joint. In the same or different frozen particle
compositions, at least one scaffold material, such as a polymer, is
administered to the joint or a substrate used for reconstructing
the joint. For example, oligopoly-ethylene glycol fumarate
optionally with a chondrocyte growth factor (e.g., fibroblast
growth factor) are included in one or more frozen particle
compositions. In the same or different frozen particle
compositions, frozen particle compositions including chondrocytes
or condrocyte progenitor cells (e.g., mesenchymal stem cells) are
administered to the joint.
In an embodiment, one or more steps of assessing the joint,
preparing the joint, debriding or abrading the joint, or
reconstructing the joint are aided by use of a computer system,
including but not limited to CT imaging, computer-aided design
(CAD), or computer-aided surgery (CAS). See, e.g., Bradley et al.,
Arch. Otolaryngol. Head Neck Surg. Vol. 34, pp. 1080-1084 (2008),
which is incorporated by reference herein.
Example 22
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents and One or More
Biological Remodeling Agents
Frozen particles containing one or more biological adhesive agents
(for example, bispecific antibodies or bispecific proteins), are
used to bind cells or tissues specifically to therapeutic targets,
such as endothelial cells, leukocytes, epithelial cells, cancer
cells, extracellular matrices, vasculature, lymphatics, tumors, and
other tissues. For example, one or more frozen particles containing
at least one bispecific receptor, antibody, ligand, or fusion
proteins of one or more of receptors, antibodies, or ligands are
used to selectively bind or adhere leukocytes, such as macrophages,
monocytes, T cells, natural killer cells (NK cells), granulocytes,
or other cells to target tissues, extracellular matrices, or other
cell types (e.g., cancer cells, endothelial cells, or epithelial
cells).
Moreover, one or more frozen particles optionally contain at least
one biological adhesive agent and at least one leukocyte in
separate sectors. In one embodiment, the sector includes a
compartment.
In one embodiment, one or more biological adhesive agent is bound
to a leukocyte (or other cell) in vitro prior to incorporation of
the cell plus biological adhesive into the one or more frozen
particle compositions. Optionally, one or more frozen particle
compositions including at least one biological adhesive or at least
one cell are delivered sequentially to a target tissue, matrix, or
cell type.
Examples of one or more biological adhesive agents are disclosed
herein at other sections, and include but are not limited to
mammalian cell surface proteins, and glycoproteins. For example,
adhesion molecules include CD44, immunoglobulin (Ig) superfamily
members, integrins, cadherins, and selectins. These or other
factors that are included in the disclosure specifically bind to
protein or macromolecule ligands (e.g., intercellular adhesion
molecule (ICAM), vascular cell adhesion molecule (VCAM),
fibronectin, and hyaluronate), MADCAM, LFA-1, and others. Other
cell surface receptors are included as biological adhesive agents,
including but not limited to immunoglobulin Fc receptors (FcR),
complement receptors (CR), and surface immunoglobulin (sIg).
Example 23
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents for Administration
to Tumor Tissue
Frozen particles containing one or more biological-based adhesive
agents are used to deliver and bind immune effector cells to
primary or metastatic tumor cells, as well as tumor-associated
stroma or extracellular matrices. Macrophages or monocytes that
have the potential to kill tumor cells, and present
tumor-associated antigens are recognized by antibodies that bind
integrin receptors, such as VLA-4, .beta.-1, .beta.-2, Fc.gamma.
receptor I (CD64) or by cell adhesion peptides (e.g., YRGDS,
YEILDV). (See, for example, Martin-Manso et al., Cancer Res., vol.
68, pp. 7090-7099 (2008); Wagner et al., Biomat., vol. 25, pp.
2247-2263 (2006); each of which is incorporated herein by
reference). In addition, lymphocytes (such as T cells or B cells),
as well as natural killer cells are capable of directed killing of
tumor cells, and are included in specific embodiments disclosed
herein.
Biological adhesive agents, including a bispecific antibody, such
as anti-CD64 binding domain (e.g., single chain Fv (SCFv)) is fused
to a second binding domain that recognizes a tumor-associated
antigen (e.g., CA-125 (mucin 16), or melanoma-associated antigen
(MAGE)). Mucin 16 binds macrophages to ovarian cancer cells, while
MAGE binds macrophages to melanoma cancer cells. Generation,
including design, construction, and production, of bispecific
antibodies is generally known in the art. (See, for example, USPTO
Application Publication No. 20080305105; Kufer et al., Trends in
Biotech., vol. 22, pp. 238-244 (2004); each of which is
incorporated herein by reference.)
Macrophage or monocyte cells are obtained from the peripheral blood
of cancer patients or subjects. Monocytes are purified from
peripheral blood leukocytes (standard reagents and protocols are
available from, for example, StemCell Tech., Inc., Vancouver, B.C.,
Canada). Monocytes are activated by treatment in vitro with
cytokines, such as interferon-.gamma.. (See, for example, Kufer et
al., Ibid.) Production of macrophage cells that are cytotoxic for
tumor cells is described, for example, in Martin-Manso et al.,
Ibid. Cytotoxic macrophage cells are bound in vitro to a bispecific
antibody (e.g., antibody that recognizes CD64 or MAGE), prior to
incorporation into one or more frozen particle compositions for
administration to a melanoma tumor.
Briefly, bispecific antibodies at 10-100 micrograms/mL in RPMI 1640
media, pH 7.4 (Invitrogen Corp., Carlsbad, Calif.), are incubated
with monocyte cells for 1-4 hours at 5.degree.-37.degree. C.
Monocyte cells with bound bispecific antibodies are washed by
centrifugation and incorporated into one or more frozen particle
compositions containing dimethylsulfoxide (10% vol/vol), RPMI 1640
media, and human serum (20% vol/vol).
One or more frozen particle compositions containing one or more
monocyte cells, one or more biological adhesive agents, and media
are delivered directly to tumor tissue by a device (for example, a
spray device). Depending on various factors, including but not
limited to, size of tumor, presence of metastatic tumor tissue,
extent of any metastatic tissue, type of tissue of origin for the
tumor, location of tumor, condition of the subject, or other
factors, the depth of frozen particle penetration can be predicted
or determined through design or alteration of frozen particle
composition velocity, size, shape, and constituency of the one or
more frozen particles.
Example 24
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents for Administration
to Tumor Tissue
Immune effector cells (including monocytes, macrophages, natural
killer cells, or lymphocytes) plus bound bispecific antibodies are
delivered to tumor tissue, for example, at a site or organ (e.g.
lung, liver) using a device (such as an endoscope, incluindg a
laparascope or thoracoscope). In one embodiment, a particle
spraying device is introduced through a trocar and guided by way of
an endoscope, delivers the frozen particle compositions including
at least one immune effector cell with at least one biological
adhesive to the target site. In one embodiment, the target site
includes tumor tissue. In at least on embodiment, the target site
includes tissue surrounding a tumor. In one embodiment, the target
site includes tissue suspected of being cancerous. In one
embodiment, the target site includes primary tumor tissue. In one
embodiment, the target site includes metastatic cancer tissue.
In one embodiment, frozen particle compositions including at least
one biological adhesive and at least one immune effector cell are
administered as an adjunct therapy following surgery to resect
diseased tissue, chemotherapy, radiation treatment, or other
therapy. For example, frozen particle compositions including at
least one biological adhesive that recognizes monocytes (e.g.,
anti-CD64) and MAGE are administered to tissue surrounding the
surgical site, including lymph nodes or sites of suspected or
anticipated metastasis.
Example 25
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents to Melanoma Cells
and Tumor-Associated Endothelial Cells
At least one biological adhesive recognizing one or more integrin
present on melanoma cells or tumor endothelial cells is used to
bind immune effector cells to melanoma cells or tumor-associated
endothelial cells. For example, one or more antibodies specific for
the integrin .alpha..sub.v.beta..sub.3 and CD3 (a signaling part of
the T cell antigen receptor) can be used in conjunction with
cytotoxic T cells derived from melanoma subjects. See, for example,
Berger et al., J. Clin. Invest. vol. 118, pp. 294-305 (2008), which
is incorporated herein by reference.
One or more frozen particle compositions containing
anti-.alpha..sub.v.beta..sub.3, anti-CD3, or cytotoxic T cells bind
to melanoma cells directly or indirectly following binding to tumor
neovasculature endothelium and extravasation. See, for example,
Mahabeleshwar et al., Ibid. In one embodiment, the one or more
frozen particle compositions are administered in multiple
dimensions (e.g., x, y, z coordinates) to melanoma cells,
neovasculature, and adjacent tissues (which may or may not be
malignant). In one embodiment, primary tumor cells, metastatic
tumor cells, neovasculature, and adjacent lymphatic ducts and lymph
nodes are targeted. One or more frozen particle compositions
delivered to the epidermis, dermis, and subcutaneous layers of a
subject target melanoma cells in radial, vertical, and metastatic
modes of growth. See, for example, Mahabeleshwar et al, Ibid.
In one embodiment, administration of the one or more frozen
particle compositions in three dimensions is conducted with a
computer-guided spraying device. The computer-guided device uses
one or more computer systems, or one or more computer programs to
derive or obtain data to predict or generate one or more frozen
particle compositions based on specific characteristics. For
example, the one or more frozen particle compositions are predicted
or generated based on particle hardness, shape, size, constituency,
or other factors. The one or more frozen particle composition
administration is predicted or generated based on number of frozen
particle compositions administered for any particular round of
delivery, the velocity of delivery, the angle of delivery, the
number of rounds of delivery of the same or different frozen
particle compositions, the type of tissue receiving the frozen
particle compositions, the condition of the tissue receiving the
frozen particle compositions, and other factors. In this manner,
the one or more frozen particle compositions are administered to a
particular target tissue, and to a particular desired depth or
breadth.
Example 26
Compositions and Methods of Administering Frozen Particles
Including One or More Biological Adhesive Agents to Melanoma
Cells
One or more frozen particle compositions including one or more
biological adhesive agents capable of specifically binding melanoma
tumor cell surface receptors, including at least one receptor
capable of signaling or initiating apoptosis are administered to
melanoma cell's. For example, at least one biological adhesive
agent including at least one bispecific protein that recognizes
melanoma tumor cell antigens (e.g., MAGE), as well as a
pro-apoptotic cell surface receptor (e.g., death receptor 5 (DR5))
is delivered to melanoma cells for induction of apoptosis.
In one embodiment, binding of DR5 by an agonistic monoclonal
antibody or apoptosis ligand 2/TNF-related apoptosis-inducing
ligand (e.g., Apo2L/TRAIL) initiates signaling that leads to
apoptotic death of the tumor cell. See, for example, Ashkenazi,
Nat. Rev. Drug Discov., vol. 7, pp. 1001-1012 (2008). Some examples
of agonistic antibodies that are capable of inducing apoptosis on
tumor cells include, but are not limited to, mapatumumab and
lexatumumab (Human Genome Sciences, Inc., Rockville, Md.; HGS),
Apomab (Genentech Inc., South San Francisco, Calif.), AMG655
(Amgen, Inc., Thousand Oaks, Calif.), CS-1008 (Daiichi Sankyo Co.,
Ltd., Tokyo), and LBY-135 (Novartis Int'l AG, Basel).
In one embodiment, a bispecific protein including anti-MAGE binding
domains (e.g., single chain Fv (SCFv)) and at least one agonistic
anti-DR5 binding domain (e.g., SCFv from Apomab; Ashkenazi, Ibid)
is administered in one or more frozen particle compositions
directly to melanoma cells, or delivered to subcutaneous layers
surround the melanoma cells.
In one embodiment, in addition to targeting primary tumor cells,
tissue known to be metastatic, or suspected to be metastatic due to
the epidemiology of the disease, are targeted. For example,
melanoma is known to metastasize to the brain. In one embodiment,
the brain receives one or more frozen particles alone or in
combination with surgery (e.g., craniotomy), based on imaging
studies done with computer-assisted tomography or magnetic
resonance imaging. Frozen particle compositions including
pro-apoptotic agonists or anti-MAGE binding proteins are used as
adjuvant therapy following surgery (e.g., open surgery,
stereotactic surgery, or stereotactic radiosurgery to remove or
destroy melanoma metastatic cells.
In one embodiment, minimally invasive computer assisted surgery is
used to remove tumor cells and tumor tissue, followed by
administration of one or more frozen particle compositions as
adjuvant therapy. For example, computer-aided surgery (CAS) is used
with stereotactic surgery systems to target tumor cells that have
infiltrated essential and/or highly vascularized brain tissues that
are considered inaccessible or inoperable by standard methods.
Example 27
Frozen Piercing Implements Utilized for Transdermal Delivery
In one embodiment, frozen hydrogen oxide piercing implements,
including microneedles, are utilized for transdermal delivery of at
least one agent.
In one embodiment, frozen microneedles with dimensions ranging from
approximately nanometers (nm) to approximately millimeters (mm) can
be made from hydrogen oxide ice Ic, and optionally include one or
more reinforcement agents. Frozen microneedles can contain at least
one therapeutic agent, including but not limited to at least one
antigen, vaccine, antibiotic, analgesic, or other agent. The use of
microneedles has been reported to induce minor skin irritation.
See, for example, Wermeling, et al., Ibid. Such minor irritation
may be desirable in certain instances (i.e. for vaccination).
In one embodiment, microneedles made of frozen hydrogen oxide, and
optionally reinforced with at least one of polylactic acid (L-PLA
from BPI at Birmingham, Ala.) or polyvinyl pyrrolidone (PVP), are
cast in a first micromold fabricated using standard
photolithography and molding processes. For example, a frozen
microneedle mastermold is created in SU-8 photoresist (SU-8 2025,
Microchem, Newton, Mass.) by UV exposure to mold, for example,
pyramidal (square cross-section) piercing implements tapering from
a base measuring approximately 4 .mu.m to approximately 300 .mu.m
in width to a tip of approximately 0.33 .mu.m to approximately 25
.mu.m in width over a length of approximately 10 .mu.m to
approximately 2.0 mm. Next a frozen piercing implement second mold
is made, for example, from polydimethylsiloxane (PDMS, Sylgard 184,
Dow Corning, Midland, Mich.) by using the first micromold. Multiple
replicate molds can be produced by layering PDMS on the second
mold. (See Lee et al, Biomaterials, vol. 29, pp. 2113-2124 (2008)
which is incorporated herein by reference.) Finally, frozen
piercing implements are made, for example, by contacting liquid
hydrogen oxide optionally containing L-PLA and at least one
therapeutic or other agent in the molds, and freezing at
-20.degree. C. to -250.degree. C. to form frozen hydrogen oxide
piercing implements, such as microneedles.
In one embodiment, the frozen hydrogen oxide piercing implements,
such as microneedles, are in one or more phases including at least
one of: amorphous solid water, low density amorphous ice, high
density amorphous ice, very high density amorphous ice, clathrate
ice, hyperquenched glassy water, ice Ic, ice II, ice III, ice IV,
ice V, ice VI, ice VII, ice VIII, ice IX, ice X, ice XI, ice XII,
ice XIII, ice XIV, or ice XV.
In one embodiment, multiple micromolds contain one or more arrays
of multiple piercing implements, including one or more
microneedles. For example, in one embodiment, an array containing
120 microneedles in rows is made in a 9.times.9 mm configuration.
See, for example, Park et al, J. Control. Rel., vol. 104, pp. 51-66
(2005) which is incorporated herein by reference.
In one embodiment, frozen piercing implement arrays, including
microneedle arrays, are made by contacting, for example, hydrogen
oxide, one or more polymers, and at least one therapeutic agent.
For example, frozen piercing implement arrays, including
microneedle arrays, are made by utilizing at least one support
structure fabricated by patterning SU-8 epoxy photoresist onto
glass substrates and defining piercing implement shapes by
lithography. In one embodiment, at least one frozen piercing
implement includes at least one side-opening hollow implement. In
one embodiment, piercing implement tips are sharpened by reactive
ion etching.
In one embodiment, hydrogen oxide frozen piercing implements, such
as microneedles, include an optional reinforcement agent, such as
L-PLA, as well as at least one therapeutic or other agent
(including but not limited to bovine serum albumin (BSA) or
lysozyme). For example, reinforced hydrogen oxide solutions with
approximately 20% (weight %) bovine serum albumin (Sigma, St.
Louis, Mo.) are frozen at approximately 0.degree. C. to
approximately -250.degree. C. or lower in the micromolds to form at
least one array of frozen piercing implements, such as
microneedles.
In one embodiment, an array with 100 piercing implements, including
microneedles, delivers about 2000 .mu.g of BSA transdermally. See,
for example, Lee et al, Ibid. In one embodiment, at least one
piercing implement of the array includes a frozen piercing
implement. In one embodiment, all of the piercing implements of the
array include frozen piercing implements.
In one embodiment, frozen piercing implement arrays, such as
microneedle arrays, including BSA are inserted by hand into the
skin, then taped in place and left for time sufficient to deliver
at least part of the at least one agent (e.g., BSA). In one
embodiment, the array is allowed to stay in contact with the
substrate for at least approximately 1 second, approximately 5
seconds, approximately 10 seconds, approximately 20 seconds,
approximately 30 seconds, approximately 45 seconds, approximately 1
minute, approximately 2 minutes, approximately 5 minutes,
approximately 10 minutes, approximately 30 minutes, approximately 1
hour, approximately 2 hours, approximately 5 hours, approximately
24 hours, or any value therebetween or greater.
In one embodiment, frozen piercing implements, such as
microneedles, are inserted and ejected or released into the skin by
at least one mechanism including, but not limited to, breaking,
applying shear force, for example with a blade, or applying axial
force, for example, with plungers or pressure through the base of
the array.
In one embodiment, frozen piercing implements, including
microneedles, in an array define at last one cavity including at
least one therapeutic or other agent (e.g. a protein, nucleic acid,
cell, viral vector, or pharmaceutical). In one embodiment, both the
support structure and at least one frozen piercing implement, such
as a microneedle, define at least one cavity including at least one
therapeutic or other agent. In one embodiment, the support
structure includes at least one reservoir in fluid communication
with at least one frozen piercing implement, or other piercing
implement of the array that includes at least one frozen piercing
implement. In one embodiment, at least one frozen piercing
implement is hollow and is in fluid communication with at least one
external reservoir.
Cavitized or hollow frozen microneedles can be created by laser
drilling holes extending the length of the microneedles projecting
away from the support structure. See, for example, Martanto et al,
Ibid.
In one embodiment, the one or more frozen piercing implements are
utilized for delivery of at least one therapeutic agent or other
agent, diagnostic or detection materials or devices, or sensing, or
collecting one or more materials from the substrate (e.g. blood,
interstitial fluid, one or more cells or biological materials). In
one embodiment, at least one pump, syringe, or other material
transfer device is included in the frozen piercing implement array.
In one embodiment, a frozen piercing implement array, such as a
microneedle array, includes a manifold for connection to a pump.
See, for example, Martanto et al, Ibid.
In one embodiment, hollow frozen piercing implements, such as
microneedles, are utilized to deliver at least one therapeutic or
other agent in vivo. For example, McAllister et al, Proc. Natl.
Acad. Sci. USA, vol. 100, pp. 13755-13760 (2003), which is
incorporated herein by reference. As reported, hollow microneedles
interfaced with a pump providing 10-14 pounds/square inch of
pressure to deliver 32 .mu.l of insulin solution (100 units/ml
Humulin-R, Eli Lilly Co., Indianapolis, Ind.) to diabetic rats. As
reported, microneedle delivery of insulin is effective, as
indicated by the reduction in blood glucose levels in diabetic rats
following treatment. Id. As reported, microneedle injection
delivery of insulin is comparable in efficacy to subcutaneous
injection of insulin with a conventional hypodermic syringe
(McAllister et al, Ibid.).
Further, as reported, solid microneedles with tapered and beveled
tips and feature sizes from 1 to 1,000 .mu.m provide increased skin
permeability by orders of magnitude for macromolecules and
particles up to 50 nm in radius. Id.
In one embodiment, frozen hydrogen oxide microneedles are coated
with at least one therapeutic or other agent configured for rapid
release subsequent to piercing a substrate, such as skin. For
example, frozen piercing implements, such as microneedles, and the
corresponding arrays, are dip-coated by immersing them in stable
aqueous solutions of at least one therapeutic, adhesive, biological
remodeling, or other agent. For example, an agent such as
sulforhodamine (Invitrogen-Molecular Probes, Eugene, Oreg.),
FITC-labeled BSA ((Invitrogen-Molecular Probes, Eugene, Oreg.),
YOYO-3-labeled plasmid DNA (Invitrogen-Molecular Probes, Eugene,
Oreg.), sodium fluorescein (Sigma-Aldrich, St. Louis, Mo.), or
pilocarpine hydrochloride (Sigma-Aldrich, St. Louis, Mo.) are
dip-coated onto microneedles or other piercing implements. See, for
example, Jiang et al, Invest. Opthal. Vis. Sci., vol. 48, pp.
4038-4043 (2007), which is incorporated herein by reference.
In one embodiment, aqueous coating solutions containing
approximately 10% (wt/vol) polyvinylpyrrolidone (Sigma-Aldrich, St.
Louis, Mo.) and one or more therapeutic agents at concentrations
ranging from approximately 0.05% (wt/vol) to approximately 10%
(wt/vol) are coated on one or more frozen piercing implements, such
as microneedles. Id. As reported, microneedles coated with
approximately 280 ng of fluorescein or approximately 1.1 .mu.g of
pilocarpine, with dimensions of approximately 500 .mu.m in length,
approximately 100 .mu.m in width, and approximately 50 .mu.m in
thickness, are effective at delivering at least some of each agent
to the eye. Id.
In one embodiment, the strength of one or more frozen piercing
implements, such as microneedles, is measured by subjecting the one
or more frozen piercing implements to an axial force (i.e. force
parallel to the long dimension of the microneedle (e.g.,
approximately 600 .mu.m) by using a displacement force test station
(Model 921 A, Tricor Systems, Elgin, IL). For example, a stress
versus strain curve is generated by measuring displacement while
the test station presses an array of microneedles or other piercing
implements against a rigid metal surface at a rate of approximately
1.1 mm/sec.
As shown in FIG. 122, strength of microneedle or other piercing
implements is indicated by a sudden drop in force at the point of
failure. See, for example, Park et al., Ibid. The maximum force
just prior to the sudden drop defines the force of the piercing
implement failure. Piercing implements, including microneedles,
with failure forces greater than the force required for penetration
of the stratus corneum are suitable for transdermal delivery.
According to published studies, microneedles containing polylactic
acid with a height of approximately 800 .mu.m and a base diameter
of approximately 200 .mu.m display a failure force of approximately
0.50 Newtons/needle, which is approximately three times greater
than the force needed for insertion into skin. See, for example,
Park et al, J. Contr. Rel., vol. 104, pp. 51-66 (2005), which is
incorporated herein by reference.
In one embodiment, experimental data and theoretical models are
utilized to predict the failure force, or fracture force, of
piercing implements, including microneedles, which depends in part
on the implement geometry. See, for example, Davis et al, J.
Biomech., vol. 37, pp. 1155-1163 (2004) which is incorporated
herein by reference. For example, experiments to measure
microneedle fracture force can be done using an axial load test
station (Scope Test 1, EnduraTEC, Minnetonka, Minn.) to drive
microneedles against a flat block of aluminum at a rate of
approximately 0.01 mm/sec until a preset displacement of
approximately 500 .mu.m is reached. Id. Based on this test, force
and displacement data are used to determine the fracture force.
Id.
For example, microneedles or other piercing implements
approximately 500 .mu.m in length with: 1) variable tip radii and
constant wall thickness of approximately 12 .mu.m, and wall angle
of 78.5.degree.; or 2) variable wall thickness and constant tip
radius of approximately 43 .mu.m and wall angle of 78.5.degree.; or
3) variable wall angle and constant tip radius of approximately 30
.mu.m and wall thickness of approximately 10 .mu.m can be used to
measure fracture force variation with piercing implement geometry.
Id. As reported, the fracture force does not necessarily depend on
microneedle tip radius, but tends to increase with increasing wall
thickness and wall angle. Id. The geometry of any particular
piercing implement can be imaged by scanning electron microscopy,
for example, in order to determine at least the base radius, tip
radius, and wall thickness. Id. The interfacial area (i.e. the
effective area of contact between the needle and the skin) can be
calculated in at least two ways: (i) annular surface area, Aa, of
the piercing implement tip can be represented as
Aa=.pi.(r.sub.tt-t.sup.2/4) where r.sub.t=outer tip radius, and
t=wall thickness, or (ii) the full cross-sectional area, Af, at the
needle tip Af=.pi.r.sup.2.sub.t, while needle wall angle .alpha.,
can be calculated as .alpha.=tan.sup.-1[(r.sub.b-r.sub.t)/h], where
r.sub.t=outer tip radius, r.sub.b=outer radius at the needle base,
t is the wall thickness, and h is the height. Id.
Moreover, analytical models or finite element models can be
developed using standard techniques, and are capable of predicting
the fracture force of a microneedle, or other piercing implement,
with a given geometry. Id. As reported, both systems predict an
increase in fracture force with increase in wall thickness or wall
angle. Id. Accordingly, analytic or finite element models can be
developed for a particular frozen piercing implement, including a
microneedle, in such a way that the fracture force exceeds the
force required for administration to at least one substrate.
In one embodiment, the penetration of dermal layers or the location
of delivery of at least one agent is visualized by using
fluorescent molecules as tracers, followed by fluorescence
microscopy and bright field microscopy. For example, according to
published studies, delivery of sulforhodamine B (Molecular Probes,
Eugene, Oreg.) with microneedle arrays into pig cadaver skin is
assessed qualitatively by histological analysis, which includes
fluorescence microscopy, to establish the distribution of
sulforhodamine in the epidermis and dermis. See, for example, Lee
et al., Ibid.
In one embodiment, epidermis from cadaver skin sections are placed
in a diffusion chamber (Permegear, Hellertown, Pa.) and the amount
of sulforhodamine passing through the epidermis following delivery
with microneedle arrays is measured by spectrofluorimetry (Lee et
al, Ibid.). For example, in vivo delivery of agents, such as
therapeutic agents, adhesive agents, biological remodeling agents,
reinforcement agents, or other agents, by microneedle arrays can be
measured by evaluating local concentrations of the agent, or plasma
concentrations of the agent, i.e. pharmacokinetic analysis.
In one embodiment, at least one agent is administered as a
component of the frozen piercing implement (or array). In one
embodiment, at least one agent is administered in conjunction with
the frozen piercing implement (or array), including sequentially,
serially, continuously, or other mode.
For example, delivery of naltrexone by a frozen piercing implement
array, such as a microneedle array, can be monitored by analyzing
plasma samples obtained at various time points following
administration. In one embodiment, plasma naltrexone concentrations
are determined by an assay, for example, employing high pressure
liquid chromatography and mass spectrometry.
For example, pharmacokinetic parameters for naltrexone (NTX) (and
its primary metabolite naltrexol (NTXOL)), following permeation
with a microneedle array and NTX delivery with a transdermal patch
are shown in Table C, adapted from Wermeling et al, Proc. Natl.
Acad. Sci. USA, vol. 105, pp. 2058-2063 (2008), which is
incorporated herein by reference. For example, pharmacokinetic
analysis includes calculation of partuclar values, such as the
steady state concentration (Css), the area under the curve (AUC),
and the time to reach steady state concentration (Tlag), some of
which can be done with computer programs. See, for example,
WinNonlin Professional, version 4.0; Pharsight, the subject matter
of which is incorporated herein by reference.
Additionally, the pharmacokinetic parameters obtained following
microneedle-enhanced transdermal delivery of NTX are comparable to
the pharmacokinetics obtained following oral administration of NTX.
See, for example, Wermeling et al, Ibid.
TABLE-US-00007 TABLE C NTX and NTXOL exposure after
microneedle-enhanced transdermal delivery Parameters NTX NTXOL Css,
ng/ml 2.5 (1.0) 0.6 (0.5) Tlag, h 1.8 (1.1) 1.4 (1.4) Cmax, ng/ml
4.5 (2.4) 1.9 (1.3) Tmax, h 8.8 (7.6) 37.5 (31.3) AUC, ng h/ml
142.9 (43.9) 39.7 (25.9) Clast, ng/ml 1.8 (1.0) 0.4 (0.6) Results
are expressed as means .+-. SD (in parentheses) for six MN-treated
subjects. C.sub.ss = concentration at steady-state condition;
T.sub.lag = time to reach steady-state condition; C.sub.max =
maximum concentration achieved; T.sub.max = time to achieve maximum
concentration; AUC.sub.0-t = area under the concentration-time
curve from time 0 to 72 h; C.sub.last = concentration at time of
patch removal after 72 h of application.
As reported, pretreatment with microneedle arrays, removal of the
microneedles, and application of transdermal patches containing NTX
results in efficient delivery of NTX and achievement of
pharmacologically active blood concentrations of NTX (2.5 ng/ml)
within two hours after applying the patch. Id. The Css is
maintained for 48 hours. Id. Without microneedle pretreatment NTX
is not detected in the plasma following application of transdermal
patches. Id. Furthermore pretreatment of cadaver epidermis samples
with microneedle arrays followed by application of test drugs such
as calcein (Sigma Chemical Co., St. Louis, Mo.), or fluorescent BSA
(Texas Red conjugated-BSA, Molecular Probes, Eugene, Oreg.)
increases the skin permeability by more than 100-fold relative to
untreated epidermis. See, for example, Park et al, Ibid.
In one embodiment, frozen piercing implement arrays, or microneedle
arrays, are fabricated to include a support structure that acts as
a reservoir for sustained agent release. For example, sustained
release of at least one agent can occur even after removal,
sublimation, or melting of the frozen piercing implements, and be
delivered via microchannels created by the piercing implement
administration. For example, as published in Lee et al, Ibid., an
array of microneedles has a support structure that contains a test
drug, such as sulforhodamine. In one embodiment, the frozen
piercing implements, such as microneedles, include sulforhodamine
and an optional reinforcement agent, such as PLA. In one
embodiment, the base of the piercing implement contains frozen
sulforhodamine, buffers and water. Accordingly, frozen piercing
implements can be made that include channels, cavities, layers or
other areas.
In one embodiment, the tip of the frozen piercing implement
includes at least one constituent in common with the base of the
implement. In one embodiment, the tip of the frozen piercing
implement is different than the base of the implement. In one
embodiment, the support structure of the microarray is also frozen.
In one embodiment, the frozen piercing implement includes at least
one component that is not frozen. In one embodiment, the frozen
piercing implement array includes at least one implement that is
not frozen. In one embodiment, the frozen piercing implement array
includes at least one implement that is frozen.
In one embodiment, a large surface area is utilized for the base of
the piercing implement. For example, a piercing implement with a
base of approximately 81 mm.sup.2 and approximately 300 .mu.m
thick, can accommodate milligram quantities of drug. See, for
example, Lee et al., Ibid. A relatively small piercing implement
array, such as a microneedle array, (for example, 7.times.7
implements) with a base composed of approximately 30% (wt %)
solution of sulforhodamine contains approximately 3 mg of
sulforhodamine. Administration of a piercing implement array with
amylopectin needles and base, and containing sulforhodamine,
results in sustained delivery of sulforhodamine across the
epidermis for about 12 hours. See, for example, Lee et al,
Ibid.
Example 28
Frozen Piercing Implements Utilized for Transdermal Delivery
In one embodiment, frozen piercing implements, such as
microneedles, include at least one non-aqueous constituent,
including but not limited to dimethyl sulfoxide, ethanol,
isopropanol, dimethyl formamide, or formaldehyde, as well as at
least one therapeutic agent. For example, using the methods
described in Lee et al, Ibid. micromolds can be constructed to
allow casting arrays of piercing implements derived from solutions
or suspensions of at least one agent in a non-aqueous solvent. For
example, in one embodiment, a therapeutic agent, such as a small
molecule (e.g. sulforhodamine (Molecular Probes, Eugene, Oreg.)), a
protein (e.g. bovine serum albumin (BSA) conjugated to Texas Red
(Molecular Probes, Eugene, Oreg.)), a nucleic acid (e.g.
gWiz.TM.luciferase plasmid DNA (6732 base pairs, Aldevron, Fargo,
ND, USA)), a viral particle (e.g. modified vaccinia virus--Ankara
(Emory University Vaccine Center, Atlanta, Ga., USA)) is suspended
or dissolved in dimethyl sulfoxide (DMSO) (freezing temperature is
approximately 18.5.degree. C. See, for example, Gill et al, J.
Control. Release, vol. 117, pp. 227-237 (2007), which is
incorporated herein by reference herein. In one embodiment, the
suspension or solution is cast in a piercing implement array mold
by using centrifugation. See, for example, Lee et al, Ibid. In one
embodiment, the piercing implements are frozen prior to, during, or
subsequent to centrifugation. Optionally, multiple layers can be
fabricated in the frozen piercing implements by repeating the
process of centrifuging/freezing and layering, then
centrifuging/freezing again.
In one embodiment, frozen piercing implement arrays, such as
microneedle arrays, with at least one frozen piercing implement
including, for example, DMSO and at least one agent, optionally
includes at least one reinforcement agent (e.g., a polymer, ceramic
particle (e.g. silica, alumina, hydroxyapatite), metal or fiber) to
increase the fracture strength of the frozen piercing
implements.
One example of a freezing method for a composite piercing implement
with increased fracture strength is described in Deville et al,
Science, vol. 311, pp. 515-518 (2006), which is incorporated herein
by reference. In one embodiment, frozen piercing implements,
including frozen microneedles, wherein at least one frozen piercing
implement includes DMSO, at least one reinforcement agent, such as
PLA, and at least one therapeutic agent, such as BSA. In one
embodiment, DMSO assists to disrupt the lipid bilayer of the
stratum corneum. Id. In one embodiment, other solvents or chemical
enhancers of skin permeability are utilized to increase efficiency
of administration of the at least one agent. See, for example,
Prausnitz et al, Nature Biotech., vol. 26, pp. 1261-1268 (2008),
which is incorporated herein by reference.
In one embodiment, frozen piercing implements, such as frozen
microneedles, include at least one frozen piercing implement
including DMSO, are utilized for delivery of viable mammalian
cells, with DMSO providing a cryoprotectant. For example, other
cryopreservatives for mammalian cells are available from
Sigma-Aldrich, St. Louis, Mo.
In one embodiment, frozen piercing implement arrays, or frozen
microneedle arrays, including at least one frozen piercing
implement that includes DMSO, is used for localized subcutaneous or
intradermal delivery of cytotoxic T cells to skin tumors for
treatment of metastatic melanoma or other skin disorders. See, for
example, Morgan et al, Science vol. 314, pp. 126-130 (2006), which
is incorporated herein by reference.
In one embodiment, frozen piercing implements, including frozen
microneedles, optionally include at least one abrasive or explosive
material. In one embodiment, the at least one abrasive or explosive
material provides additional capability for debriding bone or other
tissue, or abrading or ablating skin or other tissue. In one
embodiment, the at least one abrasive or explosive material
promotes transdermal delivery of at least one agent. For example,
frozen piercing implement arrays, such as frozen microneedle
arrays, include at least one frozen piercing implement including
carbon dioxide (CO.sub.2). In one embodiment, liquid CO.sub.2 can
be cast in microneedle molds maintained at approximately
-100.degree. C., the freezing temperature of CO.sub.2.
Some non-limiting examples of methods for measuring the insertion
force of microneedle arrays into human skin are described by Davis
et al, Ibid. In one embodiment, frozen piercing implements
including CO.sub.2 sublimate upon administration to the at least
one substrate. In one embodiment, the at least one substrate
includes skin.
In one embodiment, transdermal patches, including at least one
agent, is administered in conjunction with the frozen piercing
implement array, including the frozen microneedle array. In one
embodiment, pores or microchannels are created by frozen piercing
implements, which is amplified, for example, if the frozen piercing
implement includes at least one explosive material, such as carbon
dioxide. For example, the rapid sublimation of carbon dioxide
during administration of the frozen piercing implement array
results in a small "explosion" near the at least one substrate to
which the frozen piercing implement array is administered, which
can assist in delivery of at least one agent. For example, as
reported, transdermal delivery of naltrexone (a skin-impermeant
hydrophilic molecule) by transdermal patch remains undetected,
unless administered following administration of microneedles, when
pharmacologically active steady state levels of naltrexone are
detected. See, for example, Wermeling et al, Ibid.
Example 29
Frozen Piercing Implements, including Surgical Blades, Blade
Handles, and Scalpels
In one embodiment, at least one of a macroneedle (e.g., hypodermic
needle), surgical blade, blade handle, scalpel, scalpel blade, or
other frozen cutting instrument (including detachable blade and/or
detachable blade handle) is fashioned by utilizing at least one
frozen composition (e.g., sterile hydrogen oxide, a frozen solution
including at least one fluid and at least one agent, at least one
frozen gas, or other frozen composition). In one embodiment, the at
least one fluid composition is frozen according to methods
described herein. In one embodiment, at least one cutting
instrument changes shape as it is used with at least one substrate.
In one embodiment, at least one cutting instrument deposits at
least one agent (such as a therapeutic agent, biological remoding
agent, adhesive agent, abrasive, explosive material, or
reinforcement agent) as it is used with at least one substrate.
In one embodiment, the frozen composition includes sterile hydrogen
oxide including at least one agent, and is frozen at approximately
-196.degree. C., then raised to a temperature of approximately
-93.degree. C. to favor formation of ice Ic. See, for example,
Halbrucker et al, Ibid. In one embodiment, macroneedles, surgical
blades, or scalpels made from at least one frozen composition,
includes at least one reinforcement agents to increase hardness and
fracture strength. For example, glass fibers, silica beads,
alumina, calcium phosphate and calcium carbonate can be added to
hydrogen oxide to increase the hardness, modulus of rupture and
fracture force of frozen hydrogen oxide. See, for example, Kingery
et al, Ibid.; Kamrani et al, Ibid.; and Delville et al, Science
vol. 311, pp. 515-518 (2006), each of which is incorporated herein
by reference. In one embodiment, frozen cutting instruments are
coated with or include at least one therapeutic agent. In one
embodiment, the at least one therapeutic agent is released into the
substrate during use of the frozen cutting instrument. In one
embodiment, the substrate includes a surgical site.
For example, in one embodiment, the frozen cutting instrument is
utilized in a procedure to transplant skin on burn patients. In one
embodiment, frozen surgical blades, or other frozen cutting
instruments, are coated with or otherwise include at least one
antibiotic. Some non-limiting examples include neomycin, polymixin
B, or gramicidin. In one embodiment, at least one other agent, such
as an adhesive agent or biological remodeling agent, is included in
the frozen cutting instrument. In one embodiment, the at least one
other agent includes at least one biological remodeling agent, such
as a growth factor, (e.g. keratinocyte growth factor, vascular
endothelial growth factor A, epidermal growth factor, fibroblast
growth factors and hepatocyte growth factor) to promote the growth,
vascularization or engraftment of skin grafts, or avoid scarring or
contraction of the graft(s). See, for example, Nolte et al, Cells
Tissue Organs, vol. 187, pp. 165-176 (2008); and Colwell et al,
Plast. Reconstr. Surg., vol. 115, pp. 204-212 (2005), each of which
is incorporated herein by reference. Non-limiting examples of
methods for coating frozen cutting instruments are reported in
Jiang et al, Ibid.
In one embodiment, frozen surgical blades are made in lengths
ranging from approximately 1-10 mm to approximately 10-50 mm. In
one embodiment, the frozen surgical blades have at least one
surgical knife handle that includes at least one frozen
composition, such as hydrogen oxide, and an optional reinforcement
agent, such as metal filings or polymer fibers approximately 5 cm
to 13 cm long. Methods for casting handles of surgical knives using
two part molds are described in U.S. Pat. No. 4,846,250, which is
incorporated herein by reference.
In one embodiment, frozen surgical blades, or other frozen cutting
instruments, are made such that they terminate in at least one of a
point, rounded tip, jagged edge, serated edge, or other
configuration. In one embodiment, at least part of the length of
the entire cutting instrument includes a jagged or serated edge. In
one embodiment, at least one configuration includes one or more of
a single sharp edge, multiple sharp edges, or a continuous sharp
edge. In one embodiment, the frozen cutting instrument, such as a
frozen blade, includes at least one of a beveled edge, symmetric or
asymmetric double beveled edges, or curvilinear cutting edges. In
one embodiment, a smaller cutting edge radius is utilized, and
forms a sharper instrument.
In one embodiment, at least one abrasive or explosive material is
utilized in forming at least one surface of the cutting instrument,
in order to fabricate a rough surface.
In one embodiment, a surgical blade is made with cutting edge radii
that are approximately 5 nm to approximately 1000 nm. See, for
example, U.S. Pat. No. 6,386,952, which is incorporated herein by
reference. In one embodiment, the edges of a frozen cutting
instrument is sharpened by, for example, grinding, mechanical
abrasion, or lapping. Id. For example, various blade or other
cutting instrument profiles can be made, including but not limited
to single edge chisel, three edge chisel, slit, two edges sharp,
four edges sharp, stab, one edge sharp, keratome, one edge sharp or
crescent, curvilinear sharp edge, as well as others. See, for
example, U.S. Pat. No. 7,396,484, which is incorporated herein by
reference.
In one embodiment, frozen surgical blades or other cutting
instruments are made for specific purposes, such as opthalmic
surgery, arthroscopic, endoscopic, laparoscopic, diagnostic,
orthopedic, or plastic surgeries. See, for example, U.S. Pat. No.
6,547,802, which is incorporated herein by reference.
In one embodiment, frozen cutting instruments, such as frozen
surgical blades, are manufactured using methods that include at
least one of: machining trenches (or V-grooves) in wafers or slabs
of frozen compositions, or etching the trenches to produce sharp
cutting edges. For example, a frozen composition slab or section
can be secured on a mounting assembly and one or more trenches
(e.g. V-groove) can be machined with a router to create a groove
with any desired angle.
In one embodiment, trenches are made, for example, with a dicing
saw blade, laser system, ultrasonic machining tool, or a hot
forging process. See, for example, U.S. Pat. No. 7,396,484, Ibid.
In one embodiment, the machined frozen slab is etched with a laser
etching system to sublimate away layers of molecules from the
V-groove and to create a sharp cutting edge of uniform radius.
In one embodiment, etching is done with a laser etching system that
includes at least one of: a laser for producing a laser beam (e.g.
CO.sub.2 laser and an Er:YAG laser); a laser aiming system adapted
to aim and direct a laser beam onto the frozen slabs (optionally
including a lens to focus the laser beam and mirrors coupled to
drive devices such as servo-galvanometers); and has an optional
controller operatively coupled to the laser and laser aiming
system. See, for example, U.S. Patent Appl. Publ. No. 20080290065,
which is incorporated herein by reference. In one embodiment, the
system includes a user interface such as a USB port, a wireless
network device, a CD-ROM drive or any combination thereof, which is
optionally coupled to the controller and allows input of programmed
designs or lines for etching the frozen composition slabs. Id.
In one embodiment, one or more fluids are allowed to flow over a
cooled (including super cooled) surface (such as a metal plate),
where the fluid freezes. Prior to, during, or subsequent to such
freezing, the frozen composition can be etched, for example, with a
laser. As an optional next step, at least one agent or other
composition is allowed to flow over the frozen etched composition
(which may be in the form of frozen piercing implements, for
example), and optionally, the frozen composition is etched
again.
In one embodiment, one or more frozen surgical blades are made by
casting hydrogen oxide, or another fluid composition, optionally
with one or more reinforcements or one or more therapeutic agents
in a mold. As discussed herein at other sections, molds for casting
surgical blades are made by standard techniques, such as for
example, photolithography or molding processes. For example, a
first surgical blade mastermold is created in SU-8 photoresist
(SU-8 2025, Microchem, Newton, Mass.) by UV exposure to create a
surgical blade with a sharp point and single cutting edge. In one
embodiment, sharp point surgical blades are formed with
approximately 10 mm to approximately 50 mm in length and
approximately 4.65 mm to approximately 7.65 mm in width. See, for
example, U.S. Pat. No. 7,396,484, Ibid. and the worldwide web at
ribbil.com/fitting-dimensions.html, the content of each of which is
incorporated herein by reference.
In one embodiment, a second surgical blade master-structure is
made, for example, of polydimethylsiloxane (PDMS, Sylgard 184, Dow
Corning, Midland, Mich.) by using the first mastermold.
Additionally, multiple replicate molds are produced, for example,
by layering PDMS on the second master-structure. See, for example,
Lee et al, Biomaterials, vol. 29, pp. 2113-2124 (2008) which is
incorporated herein by reference. Finally, in one embodiment, fluid
hydrogen oxide, or another fluid composition, including at least
one reinforcement agent, such as silica, and including at least one
therapeutic agent, such as neomycin, is added to the molds and
frozen to create frozen piercing implements, such as frozen
surgical blades. In one embodiment, the cutting edge of the frozen
surgical blade can be sharpened by etching or by grinding to form
small edge radii, including approximately 5 nm to approximately
1000 nm. See, for example, U.S. Patent Appl. Publ. No. 20080290065,
Ibid.; U.S. Pat. No. 6,386,952, Ibid.; and U.S. Pat. No. 7,396,484,
Ibid., each of which is incorporated herein by reference.
In one embodiment, frozen surgical blades are die-cut, coined or
imprinted from slabs or sections of frozen hydrogen oxide, or other
frozen composition. For example, in one embodiment, surgical blades
are stamped from frozen hydrogen oxide, or other frozen
composition, by utilizing dies or stamping devices configured to
apply sufficient pressure to impress a negative image of the die
into the frozen composition. Some non-limiting examples of
imprinting methods are described, for example, in U.S. Pat. No.
7,105,103, which is incorporated herein by reference. Frozen
surgical blades manufactured by die-cutting or imprinting can be
sharpened using grinding, lapping, or etching. See, for example,
U.S. Patent Appl. Pub. No. 20080290065, Ibid.; U.S. Pat. No.
6,386,952, Ibid.; and U.S. Pat. No. 7,396,484, Ibid., each of which
is incorporated herein by reference.
In one embodiment, the frozen cutting instrument (such as a blade)
is sharpened, for example, by using cylindrical abrasive wheels
interlocked to form a nip. In one embodiment, the cutting
instrument is sharpened, for example, by utilizing grinding
assemblies mounted for rotation about parallel axes. See, for
example, U.S. Pat. No. 6,386,952, Ibid.
Example 30A
Method of Making Frozen Particle Compositions or Frozen Piercing
Implements
Frozen particle compositions, including at least one frozen or
deposited fluid, are produced from small droplets in a nonlinear
channel including at least one super hydrophobic surface. For
example, at least one fluid is sprayed as droplets, a mist, etc.
into a nonlinear channel maintained at low temperature (e.g.,
approximately -100.degree. C.), or high pressure (e.g.,
approximately 2000 bar). For example, at 2100 bar, hydrogen oxide
is 1500 times more viscous than at atmospheric pressure, which
reduces the nucleation and crystal growth rate. Droplet size is
regulated by varying nozzle or aperature size, and pressure. Fluid
droplet diameters range, for example, from nanometers to
centimeters. In one embodiment, the fluid droplets freeze or
deposit along the nonlinear channel, forming frozen particle
compositions.
In one embodiment, the frozen fluid particle compositions are
translocated to at least one compartment that contains at least one
cooling fluid with a triple point lower than the triple point of
the frozen fluid particle compositions, such that the frozen fluid
compositions are retained in solid form. In one embodiment, the
fluid droplets are translocated along the nonlinear channel, where
at least one other fluid or at least one agent is added by way of
at least one inlet. In one embodiment, the fluid compositions are
translocated to at least one compartment, wherein they combine to
form frozen particle compositions.
In one embodiment, the fluid compositions are cycled through
multiple stages of freezing or deposition, in order to layer
multiple fluids or agents, or in order to attain a particular state
(e.g., crystalline state). In one embodiment, fluid compositions
are subjected to conditions in the nonlinear channel that favor
crystalline states, thereby forming at least one frozen piercing
implement.
In one embodiment, the cooling fluid includes at least one
refrigerant or cryogenic fluid. In one embodiment, the cooling
fluid includes at least one fluid included in the frozen particle
composition or frozen piercing implement.
Example 30B
Method of Propelling or Administering Frozen Particle Compositions
or Frozen Piercing Implements
At least one frozen particle composition or frozen piercing
implement is received or retained in at least one compartment
containing one or more cooling fluids. In one embodiment, the at
least one frozen particle composition or frozen piercing implement
is formed prior to being received in the at least one compartment.
In one embodiment, the at least one frozen particle composition or
frozen piercing implement is formed by way of extrudation,
embossing, cutting, splintering, etching, molding, electrospinning,
electrospraying, gel-casting, spin-casting, or other method, and
subsequently translocated to at least one compartment.
In one embodiment, the at least one frozen particle composition or
frozen piercing implement is formed while residing in the at least
one compartment.
In one embodiment, the cooling fluid includes at least one
refrigerant or cryogenic fluid. In one embodiment, the cooling
fluid includes at least one fluid included in the frozen particle
composition or frozen piercing implement.
In one embodiment, the cooling fluid includes at least one cooling
liquid. In one embodiment, the frozen particle compositions or
frozen piercing implements are propelled out of the compartment
(e.g., by way of at least one outlet) by inducing at least one
explosion in the cooling fluid. In one embodiment, the explosion
includes flash-boiling the at least one cooling liquid. In one
embodiment, the explosion includes a boiling liquid expanding vapor
explosion (BLEVE) of the at least one cooling liquid.
The BLEVE of the cooling liquid can be calculated according to
standard techniques. For example, in FIG. 119, a diagram of the
relationship between the pressure for a substance in various phases
of liquid and gas, and the volume occupied by that substance. The
line from point A to B indicates the substance is in liquid form
and as the volume the substance occupies expands, the pressure
falls until it reaches the vapor pressure of the liquid (B) for a
particular temperature. Id. The liquid then evaporates to become a
liquid-gas mixture, and the pressure stays constant at the vapor
pressure. Eventually the substance reaches point C, where the
liquid has been converted to gas phase, and the pressure drops with
further expansion. Id.
If the pressure falls suddenly, the substance can become unstable
liquid along the line from point B to point S. Id. S is known as a
spinodal point, and the slope of the line at this point is zero
(i.e. (.differential.p/.differential.V)=0). Id. The dotted line
connects spinodal points at different temperatures, forming the
spinodal curve, and ending at the critical point. Id. During a
BLEVE, density variations develop spontaneously and homogenously
into liquid and gas regions. Id. The rise in pressure on the vapor
pressure line from point B to C occurs rapidly, and a BLEVE
results. Id.
As illustrated in FIG. 120, for carbon dioxide, conditions for
inducing a BLEVE can be calculated for a particular substance since
the entropy of the system remains constant. Id. Thus, conditions
that induce a BLEVE for any particular substance are found along
the spinodal curve for that substance, between 1 bar and the
critical point where the curve ends. Id.
In one embodiment, the cooling fluid is flash boiled. In one
embodiment, the cooling fluid is a liquid. As with all liquids,
vapor pressure increases with temperature approximately
exponentially. For example, the boiling point of nitrogen at 1 bar
is approximately 77 K (-196.degree. C.), whereas the boiling point
of nitrogen at 10 bar is approximately 103.8 K (-169.2.degree. C.).
Accordingly, pressure can be used to control reaction temperature,
and controlling pressure above a cryogenic bath, for example, via
regulators and pumps can maintain accurate temperature control.
See, for example, Downie, Industrial Gases, pp. 445-446, Blackie
Academic and Prof. (1996).
In one embodiment, the size of the outlet assists in dispersion by
altering spray cone angles, altering particle size, altering
depressurization rates, and altering mass flow rates. See, for
example, Nutter, J. Energy Res. Technol. vol. 119, no. 3 (1997),
which is incorporated herein by reference.
In one embodiment, the frozen particle compositions or frozen
piercing implements are directionally propelled for administration
to at least one substrate. For example, a handheld device, or a
hose and nozzle system can be used, with or without a carrier gas,
(e.g., air or nitrogen) under pressure, to administer the frozen
particle compositions or frozen piercing implements to at least one
substrate.
In one embodiment, the substrate includes at least one cell,
tissue, organ, structure, or device. In one embodiment, the
substrate includes at least one food product (e.g., fruit juice,
cereals, grains, sugar, soda, meat, vegetables, canned goods, baked
goods, fruits, etc.). In one embodiment, the substrate includes at
least part of a subject.
While particular aspects of the present subject matter described
herein have been shown and described, it will be apparent to those
skilled in the art that, based upon the teachings herein, changes
and modifications can be made without departing from the subject
matter described herein and its broader aspects and, therefore, the
appended claims are to encompass within their scope all such
changes and modifications as are within the true spirit and scope
of the subject matter described herein. It will be understood by
those within the art that, in general, terms used herein, and
especially in the appended claims (e.g., bodies of the appended
claims) are generally intended as "open" terms (e.g., the term
"including" should be interpreted as "including but not limited
to," the term "having" should be interpreted as "having at least,"
the term "includes" should be interpreted as "includes but is not
limited to," etc.). It will be further understood by those within
the art that if a specific number of an introduced claim recitation
is intended, such an intent will be explicitly recited in the
claim, and in the absence of such recitation no such intent is
present. For example, as an aid to understanding, the following
appended claims may contain usage of the introductory phrases "at
least one" and "one or more" to introduce claim recitations.
However, the use of such phrases should not be construed to imply
that the introduction of a claim recitation by the indefinite
articles "a" or "an" limits any particular claim containing such
introduced claim recitation to claims containing only one such
recitation, even when the same claim includes the introductory
phrases "one or more" or "at least one" and indefinite articles
such as "a" or "an" (e.g., "a" and/or "an" should typically be
interpreted to mean "at least one" or "one or more"); the same
holds true for the use of definite articles used to introduce claim
recitations. In addition, even if a specific number of an
introduced claim recitation is explicitly recited, those skilled in
the art will recognize that such recitation should typically be
interpreted to mean at least the recited number (e.g., the bare
recitation of "two recitations," without other modifiers, typically
means at least two recitations, or two or more recitations).
Furthermore, in those instances where a convention analogous to "at
least one of A, B, and C, etc." is used, in general such a
construction is intended in the sense one having skill in the art
would understand the convention (e.g., "a system having at least
one of A, B, and C" would include but not be limited to systems
that have A alone, B alone, C alone, A and B together, A and C
together, B and C together, and/or A, B, and C together, etc.). In
those instances where a convention analogous to "at least one of A,
B, or C, etc." is used, in general such a construction is intended
in the sense one having skill in the art would understand the
convention (e.g., "a system having at least one of A, B, or C"
would include but not be limited to systems that have A alone, B
alone, C alone, A and B together, A and C together, B and C
together, and/or A, B, and C together, etc.). It will be further
understood by those within the art that typically a disjunctive
word and/or phrase presenting two or more alternative terms,
whether in the description, claims, or drawings, should be
understood to contemplate the possibilities of including one of the
terms, either of the terms, or both terms unless context dictates
otherwise. For example, the phrase "A or B" will be typically
understood to include the possibilities of "A" or "B" or "A and
B."
With respect to the appended claims, those skilled in the art will
appreciate that recited operations therein may generally be
performed in any order. Also, although various operational flows
are presented in a sequence(s), it should be understood that the
various operations can be performed in other orders than those
which are illustrated, or can be performed concurrently. Examples
of such alternate orderings may include overlapping, interleaved,
interrupted, reordered, incremental, preparatory, supplemental,
simultaneous, reverse, or other variant orderings, unless context
dictates otherwise. Furthermore, terms like "responsive to,"
"related to," or other past-tense adjectives are generally not
intended to exclude such variants, unless context dictates
otherwise.
All publications and patent applications cited in this
specification are incorporated herein by reference to the extent
not inconsistent with the description herein and for all purposes
as if each individual publication or patent application were
specifically and individually indicated to be incorporated by
reference for all purposes.
* * * * *
References